Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients
Open accessAbstract
Tumor molecular profiling is a fundamental component of precision oncology, enabling the identification of genomic alterations in genes and pathways that can be targeted therapeutically. The existence of recurrent targetable alterations across distinct histologically defined tumor types, coupled with an expanding portfolio of molecularly targeted therapies, demands flexible and comprehensive approaches to profile clinically relevant genes across the full spectrum of cancers. We established a large-scale, prospective clinical sequencing initiative using a comprehensive assay, MSK-IMPACT, through which we have compiled tumor and matched normal sequence data from a unique cohort of more than 10,000 patients with advanced cancer and available pathological and clinical annotations. Using these data, we identified clinically relevant somatic mutations, novel noncoding alterations, and mutational signatures that were shared by common and rare tumor types. Patients were enrolled on genomically matched clinical trials at a rate of 11%. To enable discovery of novel biomarkers and deeper investigation into rare alterations and tumor types, all results are publicly accessible.
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KRAS and PIK3CA concomitant mutations were found in 26.7% of CRC cases in the MSK-IMPACT study.
“KRAS and PIK3CA concomitant mutations were found in 26.7% of CRC cases in the MSK-IMPACT study, although our genomic analysis showed 42% due to the small sample size31.”
From Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization (2025) · cites this paper as [31]
The Results section, “Landscape of Somatically Altered Genes” (page unavailable), reports KRAS mutations in 44% of colon adenocarcinomas and mentions recurrent PIK3CA mutations. It does not report how often the two mutations occurred together in colorectal cancer; searches for their co-occurrence and for 26.7% found no supporting passage in our copy. (LLM, conf=0.76)
Experimental — accuracy not yet measuredMSK-IMPACT is an NGS assay that can detect variants in up to 505 unique cancer genes, including EGFR, TP53, KRAS, STK11, and ALK.
“MSK-IMPACT is an NGS assay that can detect variants in up to 505 unique cancer genes, including EGFR, TP53, KRAS, STK11, and ALK.”
From A clinical benchmark of public self-supervised pathology foundation models (2025) · cites this paper as [45]
Genome-wide association studies of specific cancers or the cancer genome atlas project identified frequent mutations in genes encoding epigenetic components.
“Genome-wide association studies of specific types of cancer or from the cancer genome atlas project have identified frequent mutations in genes that encode epigenetic components 57,58,143 .”
From Advances in epigenetics link genetics to the environment and disease (2019) · cites this paper as [143]
About 20% of all malignancies have a RAS abnormality, and about 17% of solid tumours have KRAS mutations, including about 90% of pancreatic, 50% of colon and 25% of lung adenocarcinomas.
“each dataset indicates that ~20% of all malignancies have a RAS abnormality. Overall, ~17% of solid tumours have KRAS mutations, including ~90% of pancreatic, ~50% of colon and ~25% of lung adenocarcinomas16,17”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [18]
KRAS is the most frequently mutated oncogene in human malignancies.
“Known as the ‘holy grail’ of targeted cancer therapies, KRAS is the most frequently mutated oncogene in human malignancies.”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [2]
KRAS mutations are seen in 1 in 7 of all human cancers.
“KRAS is one of the most frequently mutated oncogenes in all human malignancies and is seen in 1 in 7 of all human cancers [2].”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [2]
In a KRAS (G12C)-mutated and CDKN2A-deficient xenograft model, the combination of MRTX849 and the CDK4/6 inhibitor palbociclib resulted in a significant reduction in tumor volume, showing considerable synergistic effect.
“In a KRAS (G12C)-mutated and CDKN2A-deficient xenograft model, the combination of MRTX849 and the CDK4/6 inhibitor palbociclib resulted in a significant reduction in tumor volume, showing considerable synergistic effect [42, 144, 145].”
From Targeting KRAS mutant cancers: from druggable therapy to drug resistance (2022) · cites this paper as [144]
Large-scale profiling studies in NSCLC have revealed multiple non-random patterns of co-occurring or mutually exclusive mutations, which typically vary depending on the particular oncogenic driver mutation.
“Importantly, large-scale profiling studies utilizing either whole exome sequencing or broad targeted sequencing panels in NSCLC tumors have revealed multiple non-random patterns of co-occurring or mutually exclusive mutations, which typically vary depending on the particular oncogenic driver mutation15, 34, 58–62.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [58]
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Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895 · see citing works
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455 · see citing works
Self-citationSignatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660 · see citing works
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377 · see citing works
Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration
Thorvaldsdottir, H., Robinson, J. T., & Mesirov, J. P. (2013) · Briefings in Bioinformatics · doi:10.1093/bib/bbs017 · Cited by 9,049 · see citing works
The protein kinase complement of the human genome
Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002) · Science · doi:10.1126/science.1075762 · Cited by 8,145 · see citing works
Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720 · see citing works
Comprehensive molecular characterization of gastric adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13480 · Cited by 6,498 · see citing works
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, K., Lawrence, M. S., Carter, S. L., Sivachenko, A., Jaffe, D. B., Sougnez, C. L., Gabriel, S., Meyerson, M. M., Lander, E. S., & Getz, G. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2514 · Cited by 4,838 · see citing works
Mutational landscape and significance across 12 major cancer types
Kandoth, C., McLellan, M. D., Vandin, F., Ye, K., Niu, B., Lu, C., Xie, M., Zhang, Q., McMichael, J. F., Wyczalkowski, M. A., et al. (2013) · Nature · doi:10.1038/nature12634 · Cited by 4,419 · see citing works
Integrated Genomic Characterization of Papillary Thyroid Carcinoma
Agrawal, N., Akbani, R., Aksoy, B. A., Ally, A., Arachchi, H., Asa, S. L., Auman, J. T., Balasundaram, M., Balu, S., Baylin, S. B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.050 · Cited by 3,080 · see citing works
Self-citationOncoKB: A Precision Oncology Knowledge Base
Chakravarty, D., Gao, J., Phillips, S. M., Kundra, R., Zhang, H., Wang, J., Rudolph, J. E., Yaeger, R. D., Soumerai, T. E., Nissan, M. H., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.17.00011 · Cited by 2,735 · see citing works
Self-citationDELLY: structural variant discovery by integrated paired-end and split-read analysis
Rausch, T., Zichner, T., Schlattl, A., Stütz, A. M., Beneš, V., & Korbel, J. O. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts378 · Cited by 2,384 · see citing works
The UCSC Table Browser data retrieval tool
Karolchik, D. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh103 · Cited by 2,269 · see citing works
Frampton, G. M., Fichtenholtz, A., Otto, G. A., Wang, K., Downing, S. R., He, J., Schnall-Levin, M., White, J., Sanford, E. M., An, P., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2696 · Cited by 2,157 · see citing works
Self-citationMemorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT)
Cheng, D. T., Mitchell, T. N., Zehir, A., Shah, R. H., Benayed, R., Syed, A., Chandramohan, R., Liu, Z. Y., Won, H. H., Scott, S. N., et al. (2015) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2014.12.006 · Cited by 2,119 · see citing works
Self-citationYe, K., Schulz, M. H., Long, Q., Apweiler, R., & Ning, Z. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp394 · Cited by 1,978 · see citing works
COSMIC: somatic cancer genetics at high-resolution
Forbes, S. A., Beare, D., Boutselakis, H., Bamford, S., Bindal, N., Tate, J., Cole, C. G., Ward, S., Dawson, E., Ponting, L., et al. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1121 · Cited by 1,922 · see citing works
Highly Recurrent <i>TERT</i> Promoter Mutations in Human Melanoma
Huang, F. W., Hodis, E., Xu, M. J., Kryukov, G. V., Chin, L., & Garraway, L. A. (2013) · Science · doi:10.1126/science.1229259 · Cited by 1,816 · see citing works
<i>TERT</i> Promoter Mutations in Familial and Sporadic Melanoma
Horn, S., Figl, A., Rachakonda, P. S., Fischer, C., Sucker, A., Gast, A., Kadel, S., Moll, I., Nagore, E., Hemminki, K., et al. (2013) · Science · doi:10.1126/science.1230062 · Cited by 1,799 · see citing works
Vemurafenib in Multiple Nonmelanoma Cancers with <i>BRAF</i> V600 Mutations
Hyman, D. M., Puzanov, I., Subbiah, V., Faris, J. E., Chau, I., Blay, J.-Y., Wolf, J., Raje, N. S., Diamond, E. L., Hollebecque, A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1502309 · Cited by 1,764 · see citing works
Self-citationEmerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer
Watson, P. A., Arora, V. K., & Sawyers, C. L. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4016 · Cited by 1,536 · see citing works
RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
Poulikakos, P. I., Persaud, Y., Janakiraman, M., Kong, X., Ng, C., Moriceau, G., Shi, H., Atefi, M., Titz, B., Gabay, M. T., et al. (2011) · Nature · doi:10.1038/nature10662 · Cited by 1,454 · see citing works
Self-citationEmerging landscape of oncogenic signatures across human cancers
Ciriello, G., Miller, M. L., Aksoy, B. A., Şenbabaoğlu, Y., Schultz, N. D., & Sander, C. (2013) · Nature Genetics · doi:10.1038/ng.2762 · Cited by 1,382 · see citing works
Self-citationKillela, P. J., Reitman, Z. J., Jiao, Y., Bettegowda, C., Agrawal, N., Diaz, L. A., Friedman, A. H., Friedman, H., Gallia, G. L., Giovanella, B. C., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303607110 · Cited by 1,368 · see citing works
Punctuated Evolution of Prostate Cancer Genomes
Baca, S. C., Prandi, D., Lawrence, M. S., Mosquera, J. M., Romanel, A., Drier, Y., Park, K., Kitabayashi, N., MacDonald, T. Y., Ghandi, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.021 · Cited by 1,300 · see citing works
Self-citationLindeman, N. I., Cagle, P. T., Beasley, M. B., Chitale, D. A., Dacic, S., Giaccone, G., Jenkins, R. B., Kwiatkowski, D. J., Saldivar, J.-S., Squire, J., et al. (2013) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e318290868f · Cited by 1,280 · see citing works
Self-citationESR1 ligand-binding domain mutations in hormone-resistant breast cancer
Toy, W., Shen, Y., Won, H. H., Green, B., Sakr, R. A., Will, M., Li, Z., Gala, K. P., Fanning, S. W., King, T. A., et al. (2013) · Nature Genetics · doi:10.1038/ng.2822 · Cited by 1,252 · see citing works
Self-citationActivating ESR1 mutations in hormone-resistant metastatic breast cancer
Robinson, D. R., Wu, Y.-M., Vats, P., Su, F., Lonigro, R. J., Cao, X., Kalyana-Sundaram, S., Wang, R., Ning, Y., Hodges, L., et al. (2013) · Nature Genetics · doi:10.1038/ng.2823 · Cited by 1,145 · see citing works
The landscape of kinase fusions in cancer
Stransky, N., Cerami, E., Schalm, S., Kim, J. L., & Lengauer, C. (2014) · Nature Communications · doi:10.1038/ncomms5846 · Cited by 968 · see citing works
Anchored multiplex PCR for targeted next-generation sequencing
Zheng, Z., Liebers, M. R., Zhelyazkova, B. H., Cao, Y., Panditi, D., Lynch, K. D., Chen, J., Robinson, H. E., Shim, H. S., Chmielecki, J., et al. (2014) · Nature Medicine · doi:10.1038/nm.3729 · Cited by 908 · see citing works
The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma
Davis, C., Ricketts, C. J., Wang, M., Yang, L., Cherniack, A. D., Shen, H., Buhay, C., Kang, H.-J., Kim, S. C., Fahey, C. C., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.07.014 · Cited by 844 · see citing works
Self-citationMSIsensor: microsatellite instability detection using paired tumor-normal sequence data
Niu, B., Ye, K., Zhang, Q., Lu, C., Xie, M., McLellan, M. D., Wendl, M. C., & Ding, L. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt755 · Cited by 821 · see citing works
Chang, M. T., Asthana, S., Gao, S. P., Lee, B. H., Chapman, J. S., Kandoth, C., Gao, J., Socci, N. D., Solit, D. B., Olshen, A. B., et al. (2016) · Nature Biotechnology · doi:10.1038/nbt.3391 · Cited by 808 · see citing works
Self-citationJordan, E. J., Kim, H. R., Arcila, M. E., Barron, D., Chakravarty, D., Gao, J., Chang, M. T., Ni, A., Kundra, R., Jonsson, P., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1337 · Cited by 643 · see citing works
Self-citationPersonalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study
Roychowdhury, S., Iyer, M. K., Robinson, D. R., Lonigro, R. J., Wu, Y.-M., Cao, X., Sundaram, S. K., Sam, L. T., Balbin, O. A., Quist, M. J., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3003161 · Cited by 629 · see citing works
TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas
Melo, M., da Rocha, A. G., Vinagre, J., Batısta, R., Peixoto, J., Tavares, C., Celestino, R., de Almeida, A. P., Salgado, C., Eloy, C., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3734 · Cited by 553 · see citing works
Yao, Z., Torres, N. M., Tao, A., Gao, Y., Luo, L., Li, Q., de Stanchina, E., Abdel-Wahab, O., Solit, D. B., Poulikakos, P. I., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.08.001 · Cited by 543 · see citing works
Self-citationYan, H., Killela, P. J., Reitman, Z. J., Jiao, Y., Bettegowda, C., Agrawal, N., Diaz, L. A., Friedman, A. H., Friedman, H. S., Gallia, G. L., et al. (2014) · Neuro-Oncology · doi:10.1093/neuonc/nou206.18 · Cited by 530 · see citing works
Lindeman, N. I., Cagle, P. T., Beasley, M. B., Chitale, D. A., Đačić, S., Giaccone, G., Jenkins, R. B., Kwiatkowski, D. J., Saldivar, J., Squire, J. A., et al. (2013) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2013.03.001 · Cited by 458 · see citing works
Self-citationThe landscape and therapeutic relevance of cancer-associated transcript fusions
Yoshihara, K., Wang, Q., Torres-Garcia, W., Zheng, S., Vegesna, R., Kim, H., & Verhaak, R. G. W. (2015) · Oncogene · doi:10.1038/onc.2014.406 · Cited by 450 · see citing works
Self-citationInstitutional implementation of clinical tumor profiling on an unselected cancer population
Sholl, L. M., Do, K., Shivdasani, P., Cerami, E., Dubuc, A. M., Kuo, F. C., Garcia, E. P., Jia, Y., Davineni, P., Abo, R. P., et al. (2016) · JCI Insight · doi:10.1172/jci.insight.87062 · Cited by 450 · see citing works
Meric-Bernstam, F., Brusco, L., Shaw, K., Horombe, C., Kopetz, S., Davies, M. A., Routbort, M., Piha-Paul, S. A., Janku, F., Ueno, N., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.60.4165 · Cited by 424 · see citing works
Personalized genomic analyses for cancer mutation discovery and interpretation
Jones, S., Anagnostou, V., Lytle, K., Parpart-Li, S. T., Nesselbush, M. C., Riley, D. R. J., Shukla, M., Chesnick, B., Kadan, M., Papp, E., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa7161 · Cited by 413 · see citing works
A combinatorial strategy for treating KRAS-mutant lung cancer
Manchado, E., Weissmueller, S., Morris, J. P., Chen, C.-C., Wullenkord, R., Lujambio, A., de Stanchina, E., Poirier, J. T., Gainor, J. F., Corcoran, R. B., et al. (2016) · Nature · doi:10.1038/nature18600 · Cited by 403 · see citing works
The distribution of BRAF gene fusions in solid tumors and response to targeted therapy
Ross, J. S., Wang, K., Chmielecki, J., Gay, L. M., Johnson, A., Chudnovsky, J., Yelensky, R., Lipson, D., Ali, S. M., Elvin, J. A., et al. (2015) · International Journal of Cancer · doi:10.1002/ijc.29825 · Cited by 354 · see citing works
Contribution of p53 to Metastasis
Powell, E., Piwnica-Worms, D. R., & Piwnica-Worms, H. M. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0136 · Cited by 353 · see citing works
Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA
Schrader, K. A., Cheng, D. T., Vijai, J., Prasad, M., Walsh, M. F., Zehir, A., Ni, A., Thomas, T., Benayed, R., Ashraf, A. M., et al. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.5208 · Cited by 342 · see citing works
Self-citationGenomics-Driven Oncology: Framework for an Emerging Paradigm
Garraway, L. A. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.46.8934 · Cited by 339 · see citing works
Singh, R. R., Patel, K. P., Routbort, M. J., Reddy, N. G., Barkoh, B. A., Handal, B. A., Kanagal‐Shamanna, R., Greaves, W. O., Medeiros, L. J., Aldape, K., et al. (2013) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2013.05.003 · Cited by 315 · see citing works
Whole-Exome Sequencing of Metastatic Cancer and Biomarkers of Treatment Response
Beltran, H., Eng, K., Mosquera, J. M., Sigaras, A., Romanel, A., Rennert, H., Kossaï, M., Pauli, C., Faltas, B. M., Fontugne, J., et al. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.1313 · Cited by 287 · see citing works
Self-citationStockley, T. L., Oza, A. M., Berman, H. K., Leighl, N. B., Knox, J. J., Shepherd, F. A., Chen, E. X., Krzyzanowska, M. K., Dhani, N. C., Joshua, A. M., et al. (2016) · Genome Medicine · doi:10.1186/s13073-016-0364-2 · Cited by 276 · see citing works
Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Site
Ross, J. S., Wang, K., Gay, L. M., Otto, G. A., White, E. T., Iwanik, K., Palmer, G. A., Yelensky, R., Lipson, D., Chmielecki, J., et al. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2014.216 · Cited by 248 · see citing works
Inhibition of KRAS -Driven Tumorigenicity by Interruption of an Autocrine Cytokine Circuit
Zhu, Z., Aref, A. R., Cohoon, T. J., Barbie, T. U., Imamura, Y., Yang, S., Moody, S. E., Shen, R. R., Schinzel, A. C., Thai, T. C., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0646 · Cited by 193 · see citing works
The impact of tumor profiling approaches and genomic data strategies for cancer precision medicine
Garofalo, A., Sholl, L. M., Reardon, B. M., Taylor-Weiner, A. N., Amin‐Mansour, A., Miao, D., Liu, D., Oliver, N. M., MacConaill, L. E., Ducar, M. D., et al. (2016) · Genome Medicine · doi:10.1186/s13073-016-0333-9 · Cited by 178 · see citing works
ABRA: improved coding indel detection via assembly-based realignment
Mose, L. E., Wilkerson, M. D., Hayes, D. N., Perou, C. M., & Parker, J. S. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu376 · Cited by 177 · see citing works
Piscuoglio, S., Ng, C. K. Y., Murray, M. P., Burke, K. A., Edelweiss, M., Geyer, F. C., Macedo, G. S., Inagaki, A., Papanastasiou, A. D., Martelotto, L. G., et al. (2015) · The Journal of Pathology · doi:10.1002/path.4672 · Cited by 136 · see citing works
Self-citationSchwaederle, M., Daniels, G. A., Piccioni, D. E., Fanta, P. T., Schwab, R. B., Shimabukuro, K. A., Parker, B. A., & Kurzrock, R. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-1061 · Cited by 90 · see citing works
Menzies, A. M., Yeh, I., Botton, T., Bastian, B. C., Scolyer, R. A., & Long, G. V. (2015) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12388 · Cited by 86 · see citing works
Gao, K., Li, G., Qu, Y., Wang, M., Cui, B., Ji, M., Shi, B., & Hou, P. (2015) · Oncotarget · doi:10.18632/oncotarget.6007 · Cited by 73 · see citing works
Validation of a next-generation-sequencing cancer panel for use in the clinical laboratory.
Simen, B., Yin, L., Goswami, C., Davis, K., Bajaj, R., Gong, J., Peiper, S., Johnson, E. S., & Wang, Z.-X. (2015) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2013-0710-oa · Cited by 66 · see citing works
Automated eligibility screening and monitoring for genotype-driven precision oncology trials
Eubank, M. H., Hyman, D. M., Kanakamedala, A., Gardos, S. M., Wills, J., & Stetson, P. D. (2016) · Journal of the American Medical Informatics Association · doi:10.1093/jamia/ocw020 · Cited by 30 · see citing works
Self-citationAdvancing clinical oncology through genome biology and technology
Varghese, A. M., & Berger, M. F. (2014) · Genome biology · doi:10.1186/s13059-014-0427-x · Cited by 9 · see citing works
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Tumor mutational load predicts survival after immunotherapy across multiple cancer types
Samstein, R. M., Lee, C.-H., Shoushtari, A. N., Hellmann, M. D., Shen, R., Janjigian, Y. Y., Barron, D. A., Zehir, A., Jordan, E. J., Omuro, A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0312-8 · Cited by 4,071 · see citing works
Self-citationOncogenic Signaling Pathways in The Cancer Genome Atlas
Sanchez-Vega, F., Mina, M., Armenia, J., Chatila, W. K., Luna, A., La, K. C., Dimitriadoy, S., Liu, D. L., Kantheti, H. S., Saghafinia, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.035 · Cited by 3,201 · see citing works
“Asmore genetic alterations become targetable by specific drugs, DNA sequencing is becoming part of routine clinical care (Hartmaier et al., 2017; Schram et al., 2017; Sholl et al., 2016; Zehir et al., 2017).”
BackgroundSelf-citationA view on drug resistance in cancer
Vasan, N., Baselga, J., & Hyman, D. M. (2019) · Nature · doi:10.1038/s41586-019-1730-1 · Cited by 2,770 · see citing works
Self-citationOncoKB: A Precision Oncology Knowledge Base
Chakravarty, D., Gao, J., Phillips, S. M., Kundra, R., Zhang, H., Wang, J., Rudolph, J. E., Yaeger, R. D., Soumerai, T. E., Nissan, M. H., et al. (2017) · JCO Precision Oncology · doi:10.1200/po.17.00011 · Cited by 2,735 · see citing works
Self-citationDevelopment of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic
Chan, T. A., Yarchoan, M., Jaffee, E., Swanton, C., Quezada, S. A., Stenzinger, A., & Peters, S. (2019) · Annals of Oncology · doi:10.1093/annonc/mdy495 · Cited by 2,683 · see citing works
“Over the last few years, a large number of studies have been able to map and characterize TMB variations across disease pathologies [37, 38, 53], documenting the highest levels of TMB in melanoma followed by NSCLCs and other squamous carcinomas, while leukemias and pediatric tumors show the lowest levels of TMB.”
BackgroundPatient-derived organoids model treatment response of metastatic gastrointestinal cancers
Vlachogiannis, G., Hedayat, S., Vatsiou, A., Jamin, Y., Fernández-Mateos, J., Khan, K., Lampis, A., Eason, K., Huntingford, I., Burke, R., et al. (2018) · Science · doi:10.1126/science.aao2774 · Cited by 2,096 · see citing works
<i>STK11/LKB1</i> Mutations and PD-1 Inhibitor Resistance in <i>KRAS</i> -Mutant Lung Adenocarcinoma
Skoulidis, F., Goldberg, M. E., Greenawalt, D. M., Hellmann, M. D., Awad, M. M., Gainor, J. F., Schrock, A. B., Hartmaier, R. J., Trabucco, S. E., Gay, L., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0099 · Cited by 1,641 · see citing works
Self-citationAdvances in epigenetics link genetics to the environment and disease
Cavalli, G., & Heard, E. (2019) · Nature · doi:10.1038/s41586-019-1411-0 · Cited by 1,509 · see citing works
Current and future perspectives of liquid biopsies in genomics-driven oncology
Heitzer, E., Haque, I. S., Roberts, C. E. S., & Speicher, M. R. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-018-0071-5 · Cited by 1,557 · see citing works
Rizvi, H., Sanchez-Vega, F., La, K., Chatila, W., Jonsson, P., Halpenny, D., Plodkowski, A., Long, N., Sauter, J. L., Rekhtman, N., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.75.3384 · Cited by 1,367 · see citing works
“By contrast, the use of targeted NGS to guide treatment has become increasingly routine, particularly in patients with lung cancer.(15,16,35) Furthermore, consistent with recent reports that analyzed the same patient tumors for targeted NGS and WES,(15,35) we found that TMB quantified by targeted NGS closely correlate…”
MethodResultSelf-citationPrioritization of cancer therapeutic targets using CRISPR–Cas9 screens
Behan, F. M., Iorio, F., Picco, G., Gonçalves, E., Beaver, C. M., Migliardi, G., Santos, R., Rao, Y., Sassi, F., Pinnelli, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1103-9 · Cited by 1,338 · see citing works
“Most patients however do not benefit from such targeted therapies in part due to limited knowledge of candidate targets(Zehir et al. 2017).”
Hallin, J., Engstrom, L. D., Hargis, L., Calinisan, A., Aranda, R., Briere, D. M., Sudhakar, N., Bowcut, V., Baer, B. R., Ballard, J. A., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1167 · Cited by 1,304 · see citing works
“Genetic alterations including homozygous deletion of CDKN2A or amplification of CDK4 or CCND1 comprise up to 20% of KRAS-mutated NSCLC (43).”
BackgroundInfluentialThe tumour microenvironment in pancreatic cancer — clinical challenges and opportunities
Ho, W. J., Jaffee, E. M., & Zheng, L. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0363-5 · Cited by 1,295 · see citing works
The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker
Jardim, D. L., Goodman, A., de Melo Gagliato, D., & Kurzrock, R. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.10.001 · Cited by 1,192 · see citing works
Pan-cancer whole-genome analyses of metastatic solid tumours
Priestley, P., Baber, J., Lolkema, M. P., Steeghs, N., de Bruijn, E., Shale, C., Duyvesteyn, K., Haidari, S., van Hoeck, A., Onstenk, W., et al. (2019) · Nature · doi:10.1038/s41586-019-1689-y · Cited by 1,106 · see citing works
Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., et al. (2018) · Science · doi:10.1126/science.aao4572 · Cited by 1,142 · see citing works
Self-citationHellmann, M. D., Nathanson, T., Rizvi, H., Creelan, B. C., Sanchez-Vega, F., Ahuja, A., Ni, A., Novik, J. B., Mangarin, L. M. B., Abu-Akeel, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.018 · Cited by 1,095 · see citing works
“Emerging independent sets of data have demonstrated that targeted next-generation sequencing (NGS) panels, which are already being used routinely in clinic, may provide a reasonable estimate of exonic mutation burden (Chalmers et al., 2017; Rizvi et al., 2018; Zehir et al., 2017).”
BackgroundMethodInfluentialSelf-citationLiquid biopsy enters the clinic — implementation issues and future challenges
Ignatiadis, M., Sledge, G. W., & Jeffrey, S. S. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00457-x · Cited by 1,191 · see citing works
Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy
Skoulidis, F., & Heymach, J. V. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0179-8 · Cited by 1,019 · see citing works
McGrail, D. J., Pilié, P. G., Rashid, N. U., Voorwerk, L., Slagter, M., Kok, M., Jonasch, E. W., Khasraw, M., Heimberger, A. B., Lim, B., et al. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2021.02.006 · Cited by 1,030 · see citing works
The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers
Razavi, P., Chang, M. T., Xu, G., Bandlamudi, C., Ross, D. S., Vasan, N., Cai, Y., Bielski, C. M., Donoghue, M. T. A., Jonsson, P., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.08.008 · Cited by 993 · see citing works
Self-citationHER2-targeted therapies — a role beyond breast cancer
Oh, D.-Y., & Bang, Y.-J. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0268-3 · Cited by 1,081 · see citing works
Targeting mutant p53 for efficient cancer therapy
Bykov, V. J. N., Eriksson, S. E., Bianchi, J., & Wiman, K. G. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.109 · Cited by 889 · see citing works
Molecular profiling for precision cancer therapies
Malone, E. R., Oliva, M., Sabatini, P. J. B., Stockley, T. L., & Siu, L. L. (2020) · Genome Medicine · doi:10.1186/s13073-019-0703-1 · Cited by 942 · see citing works
“MSKCC [27] 12,670 341–410 gene panels FFPE Yes 527/5009 (10.”
de Bruijn, I., Kundra, R., Mastrogiacomo, B., Tran, T. N., Sikina, L., Mazor, T., Li, X., Ochoa, A., Zhao, G., Lai, B., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-0816 · Cited by 886 · see citing works
“1) and institutional clinical genomics initiatives such as MSK-IMPACT (2), have generated data for tens of thousands of tumors.”
BackgroundSelf-citationTumor Mutational Burden as a Predictive Biomarker in Solid Tumors
Sha, D., Jin, Z., Budczies, J., Kluck, K., Stenzinger, A., & Sinicrope, F. A. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0522 · Cited by 859 · see citing works
Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer
Yaeger, R., Chatila, W. K., Lipsyc, M. D., Hechtman, J. F., Cercek, A., Sanchez-Vega, F., Jayakumaran, G., Middha, S., Zehir, A., Donoghue, M. T. A., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2017.12.004 · Cited by 858 · see citing works
“This somatic intronic mutation was specific to MSS CRC, as we did not identify the mutant allele in any other tumor type analyzed by MSK-IMPACT (n = 9,939) (Zehir et al., 2017).”
BackgroundResultInfluentialSelf-citationTumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer
Lee, S. H., Hu, W., Matulay, J. T., Silva, M. V., Owczarek, T. B., Kim, K., Chua, C. W., Barlow, L. J., Kandoth, C., Williams, A. B., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.017 · Cited by 873 · see citing works
Self-citationOoft, S. N., Weeber, F., Dijkstra, K. K., McLean, C. M., Kaing, S., van Werkhoven, E., Schipper, L., Hoes, L., Vis, D. J., van de Haar, J., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aay2574 · Cited by 813 · see citing works
The long tail of oncogenic drivers in prostate cancer
PCF/SU2C International Prostate Cancer Dream Team, Armenia, J., Wankowicz, S. A. M., Liu, D., Gao, J., Kundra, R., Reznik, E., Chatila, W. K., Chakravarty, D., Han, G. C., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0078-z · Cited by 873 · see citing works
Self-citationCoombs, C. C., Zehir, A., Devlin, S. M., Kishtagari, A., Syed, A., Jonsson, P., Hyman, D. M., Solit, D. B., Robson, M. E., Baselga, J., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.07.010 · Cited by 866 · see citing works
Self-citationTracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal
Turajlic, S., Xu, H., Litchfield, K., Rowan, A., Chambers, T., Lopez, J. I., Nicol, D. L., O’Brien, T., Larkin, J., Horswell, S. D., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.057 · Cited by 831 · see citing works
“Similar large-scale studies of metastases have been limited (Robinson et al., 2017; Zehir et al., 2017) and have not included matched primary tumors.”
Mateo, J., Chakravarty, D., Dienstmann, R., Jezdic, S., González-Pérez, A., López-Bigas, N., Ng, C. K. Y., Bedard, P. L., Tortora, G., Douillard, J.-Y., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy263 · Cited by 836 · see citing works
“Consequently, more and more patients undergo multigene sequencing of their cancer in the hope of finding genomic alterations that could effectively be targeted with matched drugs [2].”
BackgroundSelf-citationHER kinase inhibition in patients with HER2- and HER3-mutant cancers
Hyman, D. M., Piha-Paul, S. A., Won, H., Rodon, J., Saura, C., Shapiro, G. I., Juric, D., Quinn, D. I., Moreno, V., Doger, B., et al. (2018) · Nature · doi:10.1038/nature25475 · Cited by 780 · see citing works
Self-citationHigh-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants
Razavi, P., Li, B. T., Brown, D. N., Jung, B., Hubbell, E. A., Shen, R., Abida, W. M., Juluru, K., de Bruijn, I., Hou, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0652-7 · Cited by 795 · see citing works
Self-citationPI3K/Akt/mTOR Pathway and Its Role in Cancer Therapeutics: Are We Making Headway?
Peng, Y., Wang, Y., Zhou, C., Mei, W., & Zeng, C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.819128 · Cited by 775 · see citing works
“PTEN mutations occurred in 9% (888/10336) of patients in the MSK-IMPACT Clinical Sequencing Cohort,whilePTENwasaltered inonly5%(534/10194)ofpatients in China Pan-cancer Cohort (OrigiMed2020) (20, 22).”
BackgroundInfluentialGenomic Hallmarks and Structural Variation in Metastatic Prostate Cancer
Quigley, D. A., Dang, H. X., Zhao, S. G., Lloyd, P., Aggarwal, R., Alumkal, J. J., Foye, A., Kothari, V., Perry, M. D., Bailey, A. M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.039 · Cited by 733 · see citing works
Self-citationRingel, M. D., Sosa, J. A., Baloch, Z. W., Bischoff, L. A., Bloom, G., Brent, G. A., Brock, P. L., Chou, R., Flavell, R. R., Goldner, W. S., et al. (2025) · Thyroid · doi:10.1177/10507256251363120 · Cited by 833 · see citing works
A decade of clinical development of PARP inhibitors in perspective
Mateo, J., Lord, C. J., Serra, V., Tutt, A., Balmaña, J., Castroviejo-Bermejo, M., Cruz, C., Oaknin, A., Kaye, S. B., & de Bono, J. S. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz192 · Cited by 743 · see citing works
“As interest has evolved beyond gBRCA1/2 mutations, multiplexed NGS assays of both germline and somatic DNA have become the preferred tool for patient identification [53, 54].”
BackgroundTherapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing
Maynard, A., McCoach, C. E., Rotow, J. K., Harris, L., Haderk, F., Kerr, D. L., Yu, E. A., Schenk, E. L., Tan, W., Zee, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.017 · Cited by 697 · see citing works
Mechanisms and therapeutic implications of hypermutation in gliomas
Touat, M., Li, Y. Y., Boynton, A. N., Spurr, L. F., Iorgulescu, J. B., Bohrson, C. L., Cortés‐Ciriano, I., Birzu, C., Geduldig, J. E., Pelton, K., et al. (2020) · Nature · doi:10.1038/s41586-020-2209-9 · Cited by 672 · see citing works
Metastatic colorectal cancer: mechanisms and emerging therapeutics
Shin, A. E., Giancotti, F. G., & Rustgi, A. K. (2023) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2023.01.003 · Cited by 692 · see citing works
Genomic Evolution of Breast Cancer Metastasis and Relapse
Yates, L. R., Knappskog, S., Wedge, D. C., Farmery, J. H. R., González, S., Martincorena, I., Alexandrov, L. B., Loo, P. V., Haugland, H. K., Lilleng, P. K., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.005 · Cited by 666 · see citing works
“, 2015), and a pan-cancermetastasis study (Zehir et al., 2017), where mutations in these same genes are also acquired late in disease evolution.”
BackgroundInfluentialGenome doubling shapes the evolution and prognosis of advanced cancers
Bielski, C. M., Zehir, A., Penson, A. V., Donoghue, M. T. A., Chatila, W. K., Armenia, J., Chang, M. T., Schram, A. M., Jonsson, P., Bandlamudi, C., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0165-1 · Cited by 632 · see citing works
Self-citationBernard, E., Nannya, Y., Hasserjian, R. P., Devlin, S. M., Tuechler, H., Medina-Martinez, J. S., Yoshizato, T., Shiozawa, Y., Saiki, R., Malcovati, L., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1008-z · Cited by 648 · see citing works
Self-citationTranscription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach
Cuadrado, A., Manda, G., Hassan, A., Alcaraz, M. J., Barbas, C., Daiber, A., Ghezzi, P., León, R., López, M. G., Oliva, B., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014753 · Cited by 632 · see citing works
“9, we show the results from a dataset of 10,000 cancer patients (Zehir et al., 2017).”
BackgroundThe emerging clinical relevance of genomics in cancer medicine
Berger, M. F., & Mardis, E. R. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0002-6 · Cited by 627 · see citing works
Self-citationTracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid
Miller, A. M., Shah, R. H., Pentsova, E. I., Pourmaleki, M., Briggs, S. R., DiStefano, N. M., Zheng, Y., Skakodub, A., Mehta, S. A., Campos, C., et al. (2019) · Nature · doi:10.1038/s41586-019-0882-3 · Cited by 624 · see citing works
Self-citationThe PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling
Shorning, B. Y., Dass, M. S., Smalley, M. J., & Pearson, H. B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124507 · Cited by 638 · see citing works
“However, several epithelial malignancies have also been shown to express p110δ [58], and 3% of patients with head and neck, germ cell, or colorectal cancer are reported to carry a PIK3CD mutation [59].”
BackgroundNguyen, B., Fong, C. J., Luthra, A., Smith, S. A., DiNatale, R. G., Nandakumar, S., Walch, H. S., Chatila, W. K., Madupuri, R., Kundra, R., et al. (2022) · Cell · doi:10.1016/j.cell.2022.01.003 · Cited by 616 · see citing works
Self-citationMicrosatellite Instability Is Associated With the Presence of Lynch Syndrome Pan-Cancer
Latham, A. J., Srinivasan, P., Kemel, Y. M., Shia, J., Bandlamudi, C., Mandelker, D. L., Middha, S., Hechtman, J. F., Zehir, A., Dubard-Gault, M. E., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.18.00283 · Cited by 618 · see citing works
“gov identifier, NCT01775072) for tumor and matched normal DNA sequencing via MSK-IMPACT (MSK–Integrated Mutation Profiling of Actionable Cancer Targets), a clinical NGS platform FDA authorized to identify genetic variants in up to 468 cancer-related genes as well as MSI status.(10,12,17,18) Patients were enrolled betw…”
BackgroundMethodSelf-citationHarding, J. J., Nandakumar, S., Armenia, J., Khalil, D. N., Albano, M., Ly, M., Shia, J., Hechtman, J. F., Kundra, R., El Dika, I., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2293 · Cited by 602 · see citing works
“Although the direct clinical impact of prospectiveNGS forHCC clearly has less utility than in other solid tumors such as lung cancer and melanoma (49), 24% of tumors had potentially actionable alterations that could be targets for currently available FDA-approved drugs, or agents in active clinical development.”
BackgroundSelf-citationSmall molecules, big impact: 20 years of targeted therapy in oncology
Bedard, P. L., Hyman, D. M., Davids, M. S., & Siu, L. L. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30164-1 · Cited by 616 · see citing works
Self-citationReady, N., Hellmann, M. D., Awad, M. M., Otterson, G. A., Gutierrez, M., Gainor, J. F., Borghaei, H., Jolivet, J., Horn, L., Mates, M., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.18.01042 · Cited by 581 · see citing works
“Independent reports have demonstrated concordance between TMB estimated from whole-exome sequencing and TMB estimated from targeted NGS in NSCLC and across multiple solid tumors.(18,28,29) Trial Oversight The study protocol was approved by an institutional review board or independent ethics committee at each participa…”
BackgroundAbida, W., Cheng, M. L., Armenia, J., Middha, S., Autio, K. A., Vargas, H. A., Rathkopf, D., Morris, M. J., Danila, D. C., Slovin, S. F., et al. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2018.5801 · Cited by 667 · see citing works
Self-citationA rectal cancer organoid platform to study individual responses to chemoradiation
Ganesh, K., Wu, C., O’Rourke, K. P., Szeglin, B. C., Zheng, Y., Sauvé, C.-E. G., Adileh, M., Wasserman, I., Marco, M. R., Kim, A. S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0584-2 · Cited by 569 · see citing works
Self-citationThe dormant cancer cell life cycle
Phan, T. G., & Croucher, P. I. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0263-0 · Cited by 581 · see citing works
A foundation model for clinical-grade computational pathology and rare cancers detection
Vorontsov, E., Bozkurt, A., Casson, A., Shaikovski, G., Zelechowski, M., Severson, K., Zimmermann, E., Hall, J., Tenenholtz, N., Fusi, N., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03141-0 · Cited by 572 · see citing works
“…sections matching the blocks used for DNA extraction and MSK-integrated mutation profiling of actionable targets (MSK-IMPACT) sequencing 50 , the latter of which was analyzed to determine the status of genetic alterations and establish a binary label indicating the presence or absence…”
Self-citationRAF-MEK-ERK pathway in cancer evolution and treatment
Ullah, R., Yin, Q., Snell, A. H., & Wan, L. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.05.010 · Cited by 553 · see citing works
Teo, M. Y., Seier, K., Ostrovnaya, I., Regazzi, A. M., Kania, B. E., Moran, M. M., Cipolla, C. K., Bluth, M. J., Chaim, J., Al-Ahmadie, H., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.75.7740 · Cited by 544 · see citing works
“The number of mutations detected through MSK-IMPACTwas previously shown to correlate with total ML in the urothelial The Cancer Genome Atlas data set(13) and on wholeexome sequencing.(22)”
MethodResultSelf-citationMandal, R., Samstein, R. M., Lee, K.-W., Havel, J. J., Wang, H., Krishna, C., Sabio, E. Y., Makarov, V., Kuo, F., Blecua, P., et al. (2019) · Science · doi:10.1126/science.aau0447 · Cited by 549 · see citing works
Self-citationLi, B. T., Shen, R., Buonocore, D. J., Olah, Z. T., Ni, A., Ginsberg, M. S., Ulaner, G. A., Offin, M. D., Feldman, D., Hembrough, T., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.77.9777 · Cited by 557 · see citing works
“Kettering Cancer Center.(21) Patient characteristics are listed in Table 1.”
BackgroundSelf-citationClassifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations
Dankner, M., Rose, A. A. N., Rajkumar, S., Siegel, P. M., & Watson, I. R. (2018) · Oncogene · doi:10.1038/s41388-018-0171-x · Cited by 553 · see citing works
“mutations of unknown function also frequently co-occur with other known cancer driver events [31].”
BackgroundSingal, G., Miller, P. G., Agarwala, V., Li, G., Kaushik, G. N., Backenroth, D., Gossai, A., Frampton, G. M., Torres, A. Z., Lehnert, E. M., et al. (2019) · JAMA · doi:10.1001/jama.2019.3241 · Cited by 551 · see citing works
“12 Specifically, 4 sources of data were combined to develop a death data set of high sensitivity and specificity relative to standard National Death Index data: (1) EHR structured data contained within the clinical database; (2) abstracted data from EHR unstructured documents (eg, end-of-treatment notes or condolence…”
MethodThe current state of the art and future trends in RAS-targeted cancer therapies
Punekar, S. R., Velcheti, V., Neel, B. G., & Wong, K.-K. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00671-9 · Cited by 549 · see citing works
NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls
Solomon, J. P., Linkov, I., Rosado, A., Mullaney, K. A., Rosen, E. Y., Frosina, D., Jungbluth, A. A., Zehir, A., Benayed, R., Drilon, A. E. D. C., et al. (2019) · Modern Pathology · doi:10.1038/s41379-019-0324-7 · Cited by 547 · see citing works
Self-citationTargeting Aberrant RAS/RAF/MEK/ERK Signaling for Cancer Therapy
Degirmenci, U., Wang, M., & Hu, J. (2020) · Cells · doi:10.3390/cells9010198 · Cited by 542 · see citing works
Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers
Pozdeyev, N. V., Gay, L. M., Sokol, E. S., Hartmaier, R. J., Deaver, K. E., Davis, S., French, J. D., Borre, P. V., LaBarbera, D. V., Tan, A. C., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0373 · Cited by 538 · see citing works
“In general, tumor cohorts tested by high-throughput sequencing of cancer-associated genes are enriched for advanced late-stage cases (9, 10).”
BackgroundMethodInfluentialLoss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway
Li, Z., Razavi, P., Li, Q., Toy, W., Liu, B., Ping, C., Hsieh, W., Sanchez-Vega, F., Brown, D. N., Da Cruz Paula, A. F., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.11.006 · Cited by 508 · see citing works
Self-citationYang, Z., Yang, N., Ou, Q., Xiang, Y., Jiang, T., Wu, X., Bao, H., Tong, X., Wang, X., Shao, Y. W., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2310 · Cited by 542 · see citing works
“TP53 is significantlymutated in thewhole patient cohort, which is consistent with the previous report thatmore TP53mutations were observed in advanced disease (32).”
ResultAdagrasib with or without Cetuximab in Colorectal Cancer with Mutated <i>KRAS</i> G12C
Yaeger, R., Weiss, J., Pelster, M. S., Spira, A. I., Barve, M., Ou, S.-H. I., Leal, T. A., Bekaii-Saab, T. S., Paweletz, C. P., Heavey, G. A., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2212419 · Cited by 527 · see citing works
Self-citationEGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer.
Amodio, V., Yaeger, R., Arcella, P., Cancelliere, C., Lamba, S., Lorenzato, A., Arena, S., Montone, M., Mussolin, B., Bian, Y., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0187 · Cited by 504 · see citing works
“org IntroductIon The small GTPase KRAS is mutated and constitutively active in 15% of all human tumors (1).”
BackgroundSelf-citationMolecular pathogenesis and systemic therapies for hepatocellular carcinoma
Llovet, J. M., Pinyol, R., Kelley, R. K., El-Khoueiry, A., Reeves, H. L., Wang, X. W., Gores, G. J., & Villanueva, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00357-2 · Cited by 498 · see citing works
Mandelker, D. L., Zhang, L., Kemel, Y. M., Stadler, Z. K., Vijai, J., Zehir, A., Pradhan, N., Arnold, A. G., Walsh, M. F., Li, Y., et al. (2017) · JAMA · doi:10.1001/jama.2017.11137 · Cited by 513 · see citing works
Self-citationMerino, D. M., McShane, L. M., Fabrizio, D. A., Funari, V. A., Chen, S., White, J. R., Wenz, P., Baden, J. F., Barrett, J. C., Chaudhary, R., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000147 · Cited by 517 · see citing works
“13–16 20 22 25–30 There are several targeted NGS panels at different stages of development that estimate TMB.”
BackgroundSelf-citationBenayed, R., Offin, M. D., Mullaney, K. A., Sukhadia, P., Rios, K., Desmeules, P., Ptashkin, R. N., Won, H. H., Chang, J. C., Halpenny, D. F., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0225 · Cited by 490 · see citing works
“A detailed description of MSK-IMPACT workflow and data analysis is described elsewhere (21, 26).”
BackgroundMethodSelf-citationDiverse alterations associated with resistance to KRAS(G12C) inhibition
Zhao, Y., Murciano-Goroff, Y. R., Xue, J. Y., Ang, A., Lucas, J., Mai, T. T., Da Cruz Paula, A. F., Saiki, A. Y., Mohn, D., Achanta, P., et al. (2021) · Nature · doi:10.1038/s41586-021-04065-2 · Cited by 479 · see citing works
Self-citationTargeting Alterations in the RAF–MEK Pathway
Yaeger, R. D., & Corcoran, R. B. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1321 · Cited by 474 · see citing works
Self-citationKoppula, P., Lei, G., Zhang, Y., Yan, Y., Mao, C., Kondiparthi, L., Shi, J., Liu, X., Horbath, A. D., Das, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29905-1 · Cited by 477 · see citing works
Vanderwalde, A. M., Spetzler, D. B., Xiao, N., Gatalica, Z., & Marshall, J. L. (2018) · Cancer Medicine · doi:10.1002/cam4.1372 · Cited by 461 · see citing works
“Nextgeneration sequencing (NGS) was recently found to be feasible to determine MSI status, but the published techniques require the use of paired tumor and normal tissue [3, 6].”
BackgroundEarly stage NSCLC — challenges to implementing ctDNA-based screening and MRD detection
Abbosh, C., Birkbak, N. J., & Swanton, C. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0058-3 · Cited by 451 · see citing works
Odegaard, J. I., Vincent, J. J., Mortimer, S., Vowles, J. V., Ulrich, B. C., Banks, K. C., Fairclough, S. R., Zill, O. A., Sikora, M., Mokhtari, R. B., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3831 · Cited by 437 · see citing works
“6F), compatible with previously reported alteration frequencies (36, 37).”
Wander, S. A., Cohen, O., Gong, X., Johnson, G. N., Buendia-Buendia, J. E., Lloyd, M. R., Kim, D., Luo, F., Mao, P., Helvie, K. E., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1390 · Cited by 443 · see citing works
MOLI: multi-omics late integration with deep neural networks for drug response prediction
Sharifi-Noghabi, H., Zolotareva, O., Collins, C. C., & Ester, M. (2019) · Bioinformatics · doi:10.1093/bioinformatics/btz318 · Cited by 421 · see citing works
“Presently, only 11% of patients treated with precision oncology can be placed in clinical trials and only 5% of patients benefit from precision oncology (Zehir et al., 2017; Cheng et al., 2018; Marquart et al., 2018).”
BackgroundNichols, R. J., Haderk, F., Stahlhut, C., Schulze, C. J., Hemmati, G., Wildes, D., Tzitzilonis, C., Mordec, K., Marquez, A., Romero, J., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0169-1 · Cited by 415 · see citing works
The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy
Vogler, M., Braun, Y., Smith, V. M., Westhoff, M., Pereira, R. S., Pieper, N. M., Anders, M., Callens, M., Vervliet, T., Abbas, M., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02176-0 · Cited by 448 · see citing works
Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer
Suehnholz, S. P., Nissan, M. H., Zhang, H., Kundra, R., Nandakumar, S., Lu, C., Carrero, S., Dhaneshwar, A., Fernandez, N. C., Xu, B. W., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0467 · Cited by 414 · see citing works
“Cumulative technical advances have now enabled clinical sequencing panels to detect mutations and structural alterations in hundreds of cancer-associated genes at low cost using readily available archival tumor tissue or tumor-derived cell-free DNA (34–37).”
BackgroundSelf-citationAccelerating Discovery of Functional Mutant Alleles in Cancer
Chang, M. T., Shrestha-Bhattarai, T., Schram, A. M., Bielski, C. M., Donoghue, M. T. A., Jonsson, P., Chakravarty, D., Phillips, S. M., Kandoth, C., Penson, A. V., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0321 · Cited by 402 · see citing works
“The consent of these patients, acquisition of specimens, sequencing, analysis, and reporting are described in an accompanying article (8).”
Self-citationClinical actionability of molecular targets in endometrial cancer
Urick, M. E., & Bell, D. W. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0177-x · Cited by 405 · see citing works
Vanguri, R. S., Luo, J., Aukerman, A. T., Egger, J. V., Fong, C. J., Horvat, N., Pagano, A., Araujo-Filho, J. D. A. B., Geneslaw, L., Rizvi, H., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00416-8 · Cited by 395 · see citing works
Self-citationTumour lineage shapes BRCA-mediated phenotypes
Jonsson, P., Bandlamudi, C., Cheng, M. L., Srinivasan, P., Chavan, S. S., Friedman, N. D., Rosen, E. Y., Richards, A. L., Bouvier, N., Selçuklu, S. D., et al. (2019) · Nature · doi:10.1038/s41586-019-1382-1 · Cited by 404 · see citing works
Self-citationArtificial intelligence in oncology
Shimizu, H., & Nakayama, K. I. (2020) · Cancer Science · doi:10.1111/cas.14377 · Cited by 388 · see citing works
“44 However, it is necessary to clarify the association of each of these mutations with clinical phenotypes, which is currently a bottleneck for genomic medicine.”
BackgroundKlempner, S. J., Fabrizio, D. A., Bane, S., Reinhart, M. L., Peoples, T., Ali, S. M., Sokol, E. S., Frampton, G. M., Schrock, A. B., Anhorn, R., et al. (2019) · The Oncologist · doi:10.1634/theoncologist.2019-0244 · Cited by 398 · see citing works
Mammalian SWI/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic Strategies
Centore, R. C., Sandoval, G. J., Soares, L. M. M., Kadoch, C., & Chan, H. M. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.07.011 · Cited by 394 · see citing works
Parikh, A. R., Seventer, E. E. V., Siravegna, G., Hartwig, A. V., Jaimovich, A., He, Y., Kanter, K. N., Fish, M. G., Fosbenner, K. D., Miao, B., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0410 · Cited by 400 · see citing works
“In one series, up to 9% of molecular analysis may be inadequate for tissue sequencing given low tumor cellularity, DNA yield, or quality (27).”
Self-citationThe expanding landscape of ‘oncohistone’ mutations in human cancers
Nacev, B. A., Feng, L., Bagert, J. D., Lemiesz, A. E., Gao, J., Soshnev, A. A., Kundra, R., Schultz, N., Muir, T. W., & Allis, C. D. (2019) · Nature · doi:10.1038/s41586-019-1038-1 · Cited by 384 · see citing works
Self-citationGoyal, L., Shi, L., Liu, L. Y., de la Cruz, F. F., Lennerz, J. K., Raghavan, S., Leschiner, I., Elagina, L., Siravegna, G., Ng, R. W. S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0182 · Cited by 384 · see citing works
“The frequency of FGFR2 fusions in ICC is considerably higher than that reported for any other malignancy (13)(data retrieved from http://www.”
BackgroundSelf-citationMetastasis Organotropism: Redefining the Congenial Soil
Gao, Y., Bado, I. L., Wang, H., Zhang, W., Rosen, J. M., & Zhang, X. H.-F. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.04.012 · Cited by 379 · see citing works
Evolving concepts in HER2 evaluation in breast cancer: Heterogeneity, HER2-low carcinomas and beyond
Marchiò, C., Annaratone, L., Marques, A., Casorzo, L., Berrino, E., & Sapino, A. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.02.016 · Cited by 387 · see citing works
- Authors
- Zehir, A., Benayed, R., Shah, R. H., Syed, A., Middha, S., Kim, H. R., Srinivasan, P., Gao, J., Chakravarty, D., Devlin, S. M., Hellmann, M. D., Barron, D. A., Schram, A. M., Hameed, M., Dogan, S., Ross, D. S., Hechtman, J. F., DeLair, D. F., Yao, J., Mandelker, D. L., Cheng, D. T., Chandramohan, R., Mohanty, A. S., Ptashkin, R. N., Jayakumaran, G., Prasad, M., Syed, M. H., Rema, A. B., Liu, Z. Y., Nafa, K., Borsu, L., Sadowska, J., Casanova, J., Bacares, R., Kiecka, I. J., Razumova, A., Son, J. B., Stewart, L., Baldi, T., Mullaney, K. A., Al-Ahmadie, H., Vakiani, E., Abeshouse, A. A., Penson, A. V., Jonsson, P., Camacho, N., Chang, M. T., Won, H. H., Gross, B. E., Kundra, R., Heins, Z. J., Chen, H.-W., Phillips, S., Zhang, H., Wang, J., Ochoa, A., Wills, J., Eubank, M., Thomas, S. B., Gardos, S. M., Reales, D. N., Galle, J., Durany, R., Cambria, R., Abida, W., Cercek, A., Feldman, D. R., Gounder, M. M., Hakimi, A. A., Harding, J. J., Iyer, G., Janjigian, Y. Y., Jordan, E. J., Kelly, C. M., Lowery, M. A., Morris, L. G. T., Omuro, A. M., Raj, N., Razavi, P., Shoushtari, A. N., Shukla, N., Soumerai, T. E., Varghese, A. M., Yaeger, R., Coleman, J., Bochner, B., Riely, G. J., Saltz, L. B., Scher, H. I., Sabbatini, P. J., Robson, M. E., Klimstra, D. S., Taylor, B. S., Baselga, J., Schultz, N., Hyman, D. M., Arcila, M. E., Solit, D. B., Ladanyi, M., & Berger, M. F.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Berger, Michael F
- ORCID
- Zehir, Ahmet
- Benayed, Ryma
- Shah, Ronak H
- Syed, Aijazuddin
- Middha, Sumit
- Kim, Hyunjae R
- Srinivasan, Preethi
- Gao, Jianjiong
- Chakravarty, Debyani
- Devlin, Sean M
- Hellmann, Matthew D
- Schram, Alison M
- Hameed, Meera
- Ross, Dara S
- Hechtman, Jaclyn F
- DeLair, Deborah F
- Yao, JinJuan
- Mandelker, Diana L
- Mohanty, Abhinita S
- Ptashkin, Ryan N
- Jayakumaran, Gowtham
- Syed, Mustafa H
- Rema, Anoop Balakrishnan
- Borsu, Laetitia
- Sadowska, Justyna
- Casanova, Jacklyn
- Mullaney, Kerry A
- Vakiani, Efsevia
- Abeshouse, Adam A
- Penson, Alexander V
- Jonsson, Philip
- Camacho, Niedzica
- Won, Helen H
- Gross, Benjamin E
- Kundra, Ritika
- Heins, Zachary J
- Chen, Hsiao-Wei
- Phillips, Sarah
- Zhang, Hongxin
- Wang, Jiaojiao
- Ochoa, Angelica
- Thomas, Stacy B
- Gardos, Stuart M
- Reales, Dalicia N
- Galle, Jesse
- Abida, Wassim
- Cercek, Andrea
- Feldman, Darren R
- Gounder, Mrinal M
- Hakimi, A Ari
- Harding, James J
- Iyer, Gopa
- Janjigian, Yelena Y
- Jordan, Emmet J
- Kelly, Ciara M
- Lowery, Maeve A
- Morris, Luc G T
- Omuro, Antonio M
- Raj, Nitya
- Razavi, Pedram
- Shoushtari, Alexander N
- Shukla, Neerav
- Varghese, Anna M
- Yaeger, Rona
- Coleman, Jonathan
- Bochner, Bernard
- Riely, Gregory J
- Saltz, Leonard B
- Scher, Howard I
- Sabbatini, Paul J
- Robson, Mark E
- Klimstra, David S
- Taylor, Barry S
- Baselga, Jose
- Schultz, Nikolaus
- Hyman, David M
- Arcila, Maria E
- Solit, David B
- Ladanyi, Marc
- Berger, Michael F
- Venue
- Nature Medicine
- Published
- 2017-05-08
- Volume
- 23
- Issue
- 6
- Pages
- 703-713
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC5461196
- OpenAlex
- W2613362156
- Semantic Scholar
- 0a2cc8278e64eed3a0686bd57b86e7c8ba7ff4b3
- Cited by
- 3,380
- References
- 64
- Citations by year
- 2026: 188 · 2025: 306 · 2024: 344 · 2023: 419 · 2022: 418 · 2021: 485 · 2020: 498 · 2019: 380 · 2018: 265 · 2017: 65
- FWCI
- 111.17
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-08-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA204749, R01CA182587, P01CA129243, P30CA008748, P50CA092629)
- National Institute of Dental and Craniofacial Research (K08DE024774)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- metastatic cancer, mutational landscape, MSK-IMPACT, clinical sequencing, somatic mutations, copy number alterations, structural variants, mutational signatures, precision oncology, targeted therapy, biomarkers, advanced solid tumors
- MeSH terms
- DNA, Neoplasm, Feasibility Studies, Female, Humans, Male, Mutation, Neoplasm Metastasis, Neoplasms, Prospective Studies, Biomarkers, Tumor, Cohort Studies, Sequence Analysis, DNA, Genomics, Data Mining, High-Throughput Nucleotide Sequencing
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