Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity
Open accessAbstract
Mutational hotspots indicate selective pressure across a population of tumor samples, but their prevalence within and across cancer types is incompletely characterized. An approach to detect significantly mutated residues, rather than methods that identify recurrently mutated genes, may uncover new biologically and therapeutically relevant driver mutations. Here, we developed a statistical algorithm to identify recurrently mutated residues in tumor samples. We applied the algorithm to 11,119 human tumors, spanning 41 cancer types, and identified 470 somatic substitution hotspots in 275 genes. We find that half of all human tumors possess one or more mutational hotspots with widespread lineage-, position- and mutant allele-specific differences, many of which are likely functional. In total, 243 hotspots were novel and appeared to affect a broad spectrum of molecular function, including hotspots at paralogous residues of Ras-related small GTPases RAC1 and RRAS2. Redefining hotspots at mutant amino acid resolution will help elucidate the allele-specific differences in their function and could have important therapeutic implications.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
An adjacent GG region is a susceptible site for a mutation.
“However, an adjacent GG region is a susceptible site for a mutation [37,38].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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-citationIntegrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal
Gao, J., Aksoy, B. A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S. O., Sun, Y., Jacobsen, A., Sinha, R., Larsson, E., et al. (2013) · Science Signaling · doi:10.1126/scisignal.2004088 · Cited by 15,160 · see citing works
Self-citationThe control of the false discovery rate in multiple testing under dependency
Benjamini, Y., & Yekutieli, D. (2001) · The Annals of Statistics · doi:10.1214/aos/1013699998 · Cited by 10,490 · see citing works
Signatures 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
Comprehensive molecular characterization of human colon and rectal cancer
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11252 · Cited by 8,499 · see citing works
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863 · see citing works
Integrated genomic characterization of endometrial carcinoma
The Cancer Genome Atlas Research Network, & Levine, D. A. (2013) · Nature · doi:10.1038/nature12113 · Cited by 5,784 · see citing works
Mutational heterogeneity in cancer and the search for new cancer-associated genes
Lawrence, M. S., Stojanov, P., Polak, P., Kryukov, G. V., Cibulskis, K., Sivachenko, A., Carter, S. L., Stewart, C., Mermel, C. H., Roberts, S. A., et al. (2013) · Nature · doi:10.1038/nature12213 · Cited by 5,461 · 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
Self-citationDiscovery and saturation analysis of cancer genes across 21 tumour types
Lawrence, M. S., Stojanov, P., Mermel, C. H., Robinson, J. T., Garraway, L. A., Golub, T. R., Meyerson, M., Gabriel, S. B., Lander, E. S., & Getz, G. (2014) · Nature · doi:10.1038/nature12912 · Cited by 3,096 · see citing works
Comprehensive molecular characterization of urothelial bladder carcinoma
Perou, C. M. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/za09-dk57 · Cited by 2,992 · see citing works
Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia
Weng, A. P., Ferrando, A. A., Lee, W., Morris, J. P., Silverman, L. B., Sanchez-Irizarry, C., Blacklow, S. C., Look, A. T., & Aster, J. C. (2004) · Science · doi:10.1126/science.1102160 · Cited by 2,706 · see citing works
A landscape of driver mutations in melanoma
Hodis, E., Watson, I. R., Kryukov, G. V., Arold, S. T., Imielinski, M., Theurillat, J.-P., Nickerson, E., Auclair, D., Li, L., Place, C., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.024 · Cited by 2,610 · see citing works
COSMIC: exploring the world's knowledge of somatic mutations in human cancer
Forbes, S. A., Beare, D. M., Gunasekaran, P., Leung, K., Bindal, N., Boutselakis, H., Ding, M., Bamford, S., Cole, C. G., Ward, S. A., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1075 · Cited by 2,261 · see citing works
Memorial 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
Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor
McLaren, W. M., Yates, B., Ríos, D., Chen, Y., Flicek, P., & Cunningham, F. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq330 · Cited by 1,586 · see citing works
The Life History of 21 Breast Cancers
Nik-Zainal, S., Van Loo, P., Wedge, D. C., Alexandrov, L. B., Greenman, C. D., Lau, K. W., Raine, K., Jones, D., Marshall, J., Ramakrishna, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.023 · Cited by 1,443 · see citing works
Lessons from the Cancer Genome
Garraway, L. A., & Lander, E. S. (2013) · Cell · doi:10.1016/j.cell.2013.03.002 · Cited by 1,322 · see citing works
Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma
Krauthammer, M., Kong, Y., Ha, B. H., Evans, P., Bacchiocchi, A., McCusker, J. P., Cheng, E., Davis, M. J., Goh, G., Choi, M., et al. (2012) · Nature Genetics · doi:10.1038/ng.2359 · Cited by 1,191 · see citing works
Spatial and temporal diversity in genomic instability processes defines lung cancer evolution
de Bruin, E. C., McGranahan, N., Mitter, R., Salm, M., Wedge, D. C., Yates, L., Jamal-Hanjani, M., Shafi, S., Murugaesu, N., Rowan, A. J., et al. (2014) · Science · doi:10.1126/science.1253462 · Cited by 1,117 · see citing works
The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma
Allen, E. M. V., Wagle, N., Sucker, A., Treacy, D. J., Johannessen, C. M., Goetz, E. M., Place, C. S., Taylor-Weiner, A. N., Whittaker, S. R., Kryukov, G. V., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0617 · Cited by 904 · see citing works
Genome Sequencing Identifies a Basis for Everolimus Sensitivity
Iyer, G., Hanrahan, A. J., Milowsky, M. I., Al‐Ahmadie, H. A., Scott, S. N., Janakiraman, M., Pirun, M., Sander, C., Socci, N. D., Ostrovnaya, I., et al. (2012) · Science · doi:10.1126/science.1226344 · Cited by 688 · see citing works
Self-citationThe UCSC Genome Browser database: 2014 update
Karolchik, D., Barber, G. P., Casper, J., Clawson, H., Cline, M. S., Diekhans, M., Dreszer, T. R., Fujita, P. A., Guruvadoo, L., Haeussler, M., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1168 · Cited by 670 · see citing works
Self-citationCREBBP mutations in relapsed acute lymphoblastic leukaemia
Mullighan, C. G., Zhang, J., Kasper, L. H., Lerach, S., Payne-Turner, D., Phillips, L. A., Heatley, S. L., Holmfeldt, L., Collins-Underwood, J. R., Ma, J., et al. (2011) · Nature · doi:10.1038/nature09727 · Cited by 628 · see citing works
IntOGen-mutations identifies cancer drivers across tumor types
González-Pérez, A., Perez-Llamas, C., Deu-Pons, J., Tamborero, D., Schroeder, M. P., Jené-Sanz, A., Santos, A., & López-Bigas, N. (2013) · Nature Methods · doi:10.1038/nmeth.2642 · Cited by 570 · see citing works
A census of amplified and overexpressed human cancer genes
Santarius, T., SHIPLEY, J. M., Brewer, D. S., Stratton, M. R., & Cooper, C. S. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2771 · Cited by 550 · see citing works
Ihle, N. T., Byers, L. A., Kim, E. S., Saintigny, P., Lee, J. J., Blumenschein, G. R., Tsao, A., Liu, S., Larsen, J. E., Wang, J., et al. (2012) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djr523 · Cited by 532 · see citing works
Comprehensive identification of mutational cancer driver genes across 12 tumor types
Tamborero, D., González-Pérez, A., Perez-Llamas, C., Deu-Pons, J., Kandoth, C., Reimand, J., Lawrence, M. S., Getz, G. A., Bader, G. D., Li, J., et al. (2013) · Scientific Reports · doi:10.1038/srep02650 · Cited by 475 · see citing works
Self-citationMenzies, A. M., Haydu, L. E., Visintin, L., Carlino, M. S., Howle, J. R., Thompson, J. F., Kefford, R. F., Scolyer, R. A., & Long, G. V. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0052 · Cited by 434 · see citing works
Grabiner, B., Nardi, V., Birsoy, K., Possemato, R., Shen, K., Sinha, S., Jordan, A. A., Beck, A. H., & Sabatini, D. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0929 · Cited by 418 · see citing works
Measuring error rates in genomic perturbation screens: gold standards for human functional genomics
Hart, T., Brown, K. R., Sircoulomb, F., Rottapel, R. K., & Moffat, J. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145216 · Cited by 389 · see citing works
Oncogenic ERBB3 mutations in human cancers.
Jaiswal, B. S., Kljavin, N. M., Stawiski, E. W., Chan, E., Parikh, C., Durinck, S., Chaudhuri, S., Pujara, K., Guillory, J., Edgar, K. A., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.04.012 · Cited by 350 · see citing works
Vivanco, I., Robins, H. I., Rohle, D., Campos, C., Grommes, C., Nghiemphu, P. L., Kubek, S., Oldrini, B., Chheda, M. G., Yannuzzi, N. A., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0284 · Cited by 343 · see citing works
The mutational landscapes of genetic and chemical models of Kras-driven lung cancer
Westcott, P. M. K., Halliwill, K. D., To, M. D., Rashid, M., Rust, A. G., Keane, T., Delrosario, R., Jen, K., Gurley, K. E., Kemp, C. J., et al. (2014) · Nature · doi:10.1038/nature13898 · Cited by 333 · see citing works
Genomic and Biological Characterization of Exon 4 KRAS Mutations in Human Cancer
Janakiraman, M., Vakiani, E., Zeng, Z., Pratilas, C. A., Taylor, B. S., Chitale, D., Halilovic, E., Wilson, M., Huberman, K., Ricarte Filho, J. C., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0192 · Cited by 290 · see citing works
Self-citationMutation-Specific RAS Oncogenicity Explains NRAS Codon 61 Selection in Melanoma
Burd, C. E., Liu, W., Huynh, M. V., Waqas, M. A., Gillahan, J. E., Clark, K. S., Fu, K., Martin, B. L., Jeck, W. R., Souroullas, G. P., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0729 · Cited by 214 · see citing works
Garassino, M. C., Marabese, M., Rusconi, P., Rulli, E., Martelli, O., Farina, G., Scanni, A., & Broggini, M. (2011) · Annals of Oncology · doi:10.1093/annonc/mdq680 · Cited by 185 · see citing works
Ras and relatives—job sharing and networking keep an old family together
Ehrhardt, A., Ehrhardt, G. R. A., Guo, X., & Schrader, J. W. (2002) · Experimental Hematology · doi:10.1016/s0301-472x(02)00904-9 · Cited by 184 · see citing works
The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF
Watson, I. R., Li, L., Cabeceiras, P. K., Mahdavi, M., Gutschner, T., Genovese, G., Wang, G., Fang, Z., Tepper, J. M., Stemke‐Hale, K., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1232-t · Cited by 167 · see citing works
Recurrent point mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma
Lee, C. S., Bhaduri, A., Mah, A., Johnson, W. L., Ungewickell, A., Aros, C. J., Nguyen, C. B., Rios, E. J., Siprashvili, Z., Straight, A., et al. (2014) · Nature Genetics · doi:10.1038/ng.3091 · Cited by 143 · see citing works
Prognostic Impact of KRAS Mutation Subtypes in 677 Patients with Metastatic Lung Adenocarcinomas
Yu, H. A., Sima, C. S., Shen, R., Kass, S. L., Gainor, J. F., Shaw, A. T., Hames, M. L., Iams, W. T., Aston, J. L., Lovly, C. M., et al. (2014) · Journal of Thoracic Oncology · doi:10.1097/jto.0000000000000432 · Cited by 137 · see citing works
Al‐Ahmadie, H. A., Iyer, G., Hohl, M., Asthana, S., Inagaki, A., Schultz, N. D., Hanrahan, A. J., Scott, S. N., Brannon, A. R., McDermott, G. C., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0380 · Cited by 120 · see citing works
Self-citationCheung, L. W. T., Yu, S., Zhang, D., Li, J., Ng, P. K., Panupinthu, N., Mitra, S., Ju, Z., Yu, Q., Liang, H., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.08.017 · Cited by 99 · see citing works
Clark, G. J., Kinch, M. S., Gilmer, T. M., Burridge, K., & Der, C. J. (1996) · PubMed · Cited by 88 · see citing works
Rosário, M., Paterson, H. F., & Marshall, C. J. (1999) · The EMBO Journal · doi:10.1093/emboj/18.5.1270 · Cited by 83 · see citing works
Oncogenic PIK3CA mutations in colorectal cancers and polyps
Whitehall, V., Rickman, C., Bond, C., Ramsnes, I., Greco, S. A., Umapathy, A., McKeone, D., Faleiro, R. J., Buttenshaw, R. L., Worthley, D. L., et al. (2011) · International Journal of Cancer · doi:10.1002/ijc.26440 · Cited by 81 · see citing works
Bao, L., Pu, M., & Messer, K. S. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt759 · Cited by 72 · see citing works
Rosário, M., Paterson, H. F., & Marshall, C. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.11.3750-3762.2001 · Cited by 66 · see citing works
Rong, R., He, Q., Liu, Y., Sheikh, M. S., & Huang, Y. K. (2002) · Oncogene · doi:10.1038/sj.onc.1205154 · Cited by 59 · see citing works
Barker, K. T., & Crompton, M. (1998) · British Journal of Cancer · doi:10.1038/bjc.1998.490 · Cited by 58 · see citing works
Huang, Y., Saez, R., Chao, L., Santos, E., Aaronson, S. A., & Chan, A. M.-L. (1995) · PubMed · Cited by 49 · see citing works
Signaling Pathways Regulating TC21-induced Tumorigenesis
Erdogan, M., Pozzi, A., Bhowmick, N. A., Moses, H. L., & Zent, R. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703037200 · Cited by 40 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [50]Cheng DT MSK-IMPACT: A hybridization capture-based next generation sequencing clinical assay for solit tumor molecular oncology J. Mol. Diagn 2015 In press PMC5808190 25801821
Cited by
Sorted by citations
Zehir, A., Benayed, R., Shah, R. H., Syed, A., Middha, S., Kim, H. R., Srinivasan, P., Gao, J., Chakravarty, D., Devlin, S. M., et al. (2017) · Nature Medicine · doi:10.1038/nm.4333 · Cited by 3,380 · 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
Self-citationAACR Project GENIE: Powering Precision Medicine through an International Consortium
The AACR Project GENIE Consortium, The AACR Project GENIE Consortium, André, F., Arnedos, M., Baras, A. S., Baselga, J., Bedard, P. L., Berger, M. F., Bierkens, M., Calvo, F., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0151 · Cited by 1,964 · see citing works
Self-citationGenomic correlates of clinical outcome in advanced prostate cancer
Abida, W., Cyrta, J., Heller, G., Prandi, D., Armenia, J., Coleman, I., Cieslik, M., Benelli, M., Robinson, D., Van Allen, E. M., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902651116 · Cited by 1,372 · see citing works
Self-citationClinical 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
Self-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-citationA Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations
Zhang, Y., Kwok-Shing Ng, P., Kucherlapati, M., Chen, F., Liu, Y., Tsang, Y. H., de Velasco, G., Jeong, K. J., Akbani, R., Hadjipanayis, A., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.04.013 · Cited by 626 · see citing works
Jordan, 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-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
Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS
Yao, Z., Yaeger, R., Rodrik-Outmezguine, V. S., Tao, A., Torres, N. M., Chang, M. T., Drosten, M., Zhao, H., Cecchi, F., Hembrough, T., et al. (2017) · Nature · doi:10.1038/nature23291 · Cited by 562 · see citing works
Self-citationTeo, 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
Self-citationLoss 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-citationOrganoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies
Nuciforo, S., Fofana, I., Matter, M. S., Blumer, T., Calabrese, D., Boldanova, T., Piscuoglio, S., Wieland, S., Ringnalda, F., Schwank, G., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.001 · Cited by 473 · see citing works
“Mutations affecting hotspot residues (Chang et al., 2016; Gao et al., 2017) were annotated.”
BackgroundMakohon-Moore, A. P., Zhang, M., Reiter, J. G., Bozic, I., Allen, B., Kundu, D., Chatterjee, K., Wong, F., Jiao, Y., Kohutek, Z. A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3764 · Cited by 403 · see citing works
A model for RAS mutation patterns in cancers: finding the sweet spot
Li, S., Balmain, A., & Counter, C. M. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0076-6 · Cited by 384 · see citing works
Boehm, K. M., Aherne, E. A., Ellenson, L., Nikolovski, I., Alghamdi, M., Vázquez-García, I., Zamarin, D., Long Roche, K., Liu, Y., Patel, D., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00388-9 · Cited by 357 · see citing works
Self-citationUSP7 small-molecule inhibitors interfere with ubiquitin binding.
Kategaya, L., Di Lello, P., Rougé, L., Pastor, R., Clark, K. R., Drummond, J., Kleinheinz, T., Lin, E., Upton, J.-P., Prakash, S., et al. (2017) · Nature · doi:10.1038/nature24006 · Cited by 333 · see citing works
Self-citationIntegrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages
Ng, C. K. Y., Dazert, E., Boldanova, T., Coto-Llerena, M., Nuciforo, S., Ercan, C., Suslov, A., Meier, M.-A., Bock, T., Schmidt, A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29960-8 · Cited by 165 · see citing works
Conditional Selection of Genomic Alterations Dictates Cancer Evolution and Oncogenic Dependencies
Mina, M., Raynaud, F., Tavernari, D., Battistello, E., Sungalee, S., Saghafinia, S., Laessle, T., Sanchez-Vega, F., Schultz, N., Oricchio, E., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.06.010 · Cited by 129 · see citing works
Self-citationFischer, C. G., Beleva Guthrie, V., Braxton, A. M., Zheng, L., Wang, P., Song, Q., Griffin, J. F., Chianchiano, P. E., Hosoda, W., Niknafs, N., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.06.001 · Cited by 129 · see citing works
Precancerous neoplastic cells can move through the pancreatic ductal system
Makohon-Moore, A. P., Matsukuma, K., Zhang, M., Reiter, J. G., Gerold, J. M., Jiao, Y., Sikkema, L., Attiyeh, M. A., Yachida, S., Sandone, C., et al. (2018) · Nature · doi:10.1038/s41586-018-0481-8 · Cited by 120 · see citing works
Development of genome-derived tumor type prediction to inform clinical cancer care
Penson, A., Camacho, N., Zheng, Y., Varghese, A. M., Al-Ahmadie, H., Razavi, P., Chandarlapaty, S., Vallejo, C. E., Vakiani, E., Gilewski, T., et al. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2019.3985 · Cited by 115 · see citing works
Self-citationPantsar, T., Rissanen, S., Dauch, D., Laitinen, T., Vattulainen, I., & Poso, A. (2018) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1006458 · Cited by 85 · see citing works
Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers
Kobayashi, Y., Chhoeu, C., Li, J., Price, K. S., Kiedrowski, L. A., Hutchins, J. L., Hardin, A. I., Wei, Z., Hong, F., Bahcall, M., et al. (2022) · Nature · doi:10.1038/s41586-022-04451-4 · Cited by 56 · see citing works
Xu, J., Reznik, E., Lee, H.-J., Gundem, G., Jonsson, P., Sarungbam, J., Bialik, A., Sanchez-Vega, F., Creighton, C. J., Hoekstra, J., et al. (2019) · eLife · doi:10.7554/elife.38986 · Cited by 43 · see citing works
Self-citationComputed cancer interactome explains the effects of somatic mutations in cancers
Zhang, J., Pei, J., Durham, J., Bos, T., & Cong, Q. (2022) · Protein Science · doi:10.1002/pro.4479 · Cited by 31 · see citing works
HER3 Alterations in Cancer and Potential Clinical Implications
Kilroy, M. K., Park, S., Feroz, W., Patel, H., Mishra, R., Alanazi, S., & Garrett, J. T. (2022) · Cancers · doi:10.3390/cancers14246174 · Cited by 21 · see citing works
Zhong, G., Zhao, Y., Zhuang, D., Chung, W. K., & Shen, Y. (2025) · Nature Communications · doi:10.1038/s41467-025-62318-4 · Cited by 15 · see citing works
Ecker, B. L., Court, C. M., Janssen, Q. P., Tao, A. J., D’Angelica, M. I., Drebin, J. A., Gonen, M., O’Reilly, E. M., Jarnagin, W. R., Wei, A. C., et al. (2022) · Journal of the American College of Surgeons · doi:10.1097/xcs.0000000000000212 · Cited by 13 · see citing works
Hescheler, D. A., Plum, P. S., Zander, T., Quaas, A., Korenkov, M., Gassa, A., Michel, M., Bruns, C. J., & Alakus, H. (2020) · Gastric Cancer · doi:10.1007/s10120-020-01045-9 · Cited by 12 · see citing works
Bioinformatic Identification of TP53 Gene Mutation Hotspots in Colorectal Cancer
Kovács, Z., Sugimura, H., György, T. A., Osvath, E., Manirakiza, F., & Gurzu, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126612 · Cited by 5 · see citing works
An interpretable molecular framework for predicting cancer driver missense mutations
Yang, Y., Sun, W., Liu, Y., Zhang, J., & Li, M. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2524289123 · Cited by 3 · see citing works
- Authors
- 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., Schultz, N., & Taylor, B. S.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of California, San Francisco (US)
- Corresponding author
- Taylor, Barry S
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2015-11-30
- Volume
- 34
- Issue
- 2
- Pages
- 155-163
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4744099
- OpenAlex
- W2253928581
- Cited by
- 808
- References
- 52
- Citations by year
- 2026: 41 · 2025: 72 · 2024: 73 · 2023: 67 · 2022: 89 · 2021: 91 · 2020: 92 · 2019: 89 · 2018: 102 · 2017: 70 · 2016: 18 · 2015: 1
- FWCI
- 21.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Sontag Foundation
- Cycle for Survival (P30 CA008748)
- National Institutes of Health (CA008748)
- Marie-Josée and Henry R. Kravis Center for Molecular Oncology (P30-CA008748)
- National Cancer Institute (P30-CA82103, P30CA008748, P30CA082103)
- National Institute of General Medical Sciences (T32GM007175)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- recurrent mutations, mutational hotspots, somatic mutations, driver mutations, mutational specificity, Rac1, RRAS2, cancer genomics
- MeSH terms
- Algorithms, DNA Mutational Analysis, Humans, Mutation, Neoplasms, Computational Biology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
