Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution
Open accessAbstract
Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼ 7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity.
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Glioblastoma involves deregulation of P53 and cell cycle signalling pathways.
“The disease involves deregulation of P53 and cell cycle signalling pathways1, 2, 3, 4.”
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Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
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
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · 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
Self-citationRadiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043330 · Cited by 21,807 · see citing works
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,380 · 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
Self-citationIntratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113205 · Cited by 7,774 · cited 2× · see citing works
“…theepidermal growth factor receptor variant III (EGFRvIII) led to an improved overall survival time among patients with GBM; however, 82% of these patients lost EGFRvIII expression when the tumor recurred, which suggests a competitive advantage for non-EGFRvIII expressing clones in these tumors…”
BackgroundMethodVerhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.020 · Cited by 7,575 · see citing works
Self-citationGlioma stem cells promote radioresistance by preferential activation of the DNA damage response
Bao, S., Wu, Q., McLendon, R. E., Hao, Y., Shi, Q., Hjelmeland, A. B., Dewhirst, M. W., Bigner, D. D., & Rich, J. N. (2006) · Nature · doi:10.1038/nature05236 · Cited by 6,363 · 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
Self-citationThe Somatic Genomic Landscape of Glioblastoma
Brennan, C. W., Verhaak, R. G. W., McKenna, A., Campos, B., Noushmehr, H., Salama, S. R., Zheng, S., Chakravarty, D., Sanborn, J. Z., Berman, S. H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.034 · Cited by 5,016 · see citing works
Self-citationSensitive 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
Self-citationWen, P. Y., & Kesari, S. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0708126 · Cited by 4,200 · see citing works
Mermel, C. H., Schumacher, S. E., Hill, B., Meyerson, M. M., Beroukhim, R., & Getz, G. A. (2011) · Genome biology · doi:10.1186/gb-2011-12-4-r41 · Cited by 3,469 · see citing works
Self-citationGreaves, M., & Maley, C. C. (2012) · Nature · doi:10.1038/nature10762 · Cited by 3,162 · see citing works
Tumour evolution inferred by single-cell sequencing
Navin, N., Kendall, J., Troge, J., Andrews, P., Rodgers, L., McIndoo, J., Cook, K., Stepansky, A., Levy, D., Esposito, D., et al. (2011) · Nature · doi:10.1038/nature09807 · Cited by 2,598 · see citing works
Identification of a CpG Island Methylator Phenotype that Defines a Distinct Subgroup of Glioma
Noushmehr, H., Weisenberger, D. J., Diefes, K., Phillips, H. S., Pujara, K., Berman, B. P., Pan, F., Pelloski, C. E., Sulman, E. P., Bhat, K. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.03.017 · Cited by 2,337 · see citing works
Self-citationCircular binary segmentation for the analysis of array-based DNA copy number data
Olshen, A. B., Venkatraman, E. S., Lucito, R., & Wigler, M. H. (2004) · Biostatistics · doi:10.1093/biostatistics/kxh008 · Cited by 2,256 · see citing works
Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
Ding, L., Ley, T. J., Larson, D. E., Miller, C. A., Koboldt, D. C., Welch, J. S., Ritchey, J. K., Young, M. A., Lamprecht, T., McLellan, M. D., et al. (2012) · Nature · doi:10.1038/nature10738 · Cited by 1,993 · see citing works
The clonal and mutational evolution spectrum of primary triple-negative breast cancers
Shah, S. P., Roth, A., Goya, R., Oloumi, A., Ha, G., Zhao, Y., Turashvili, G., Ding, J., Tse, K., Haffari, G., et al. (2012) · Nature · doi:10.1038/nature10933 · Cited by 1,967 · see citing works
Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics
Sottoriva, A., Spiteri, I., Piccirillo, S. G. M., Touloumis, A., Collins, V. P., Marioni, J. C., Curtis, C., Watts, C., & Tavaré, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219747110 · Cited by 1,737 · 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
Evolution and impact of subclonal mutations in chronic lymphocytic leukemia
Landau, D. A., Carter, S. L., Stojanov, P., McKenna, A., Stevenson, K., Lawrence, M. S., Sougnez, C., Stewart, C., Sivachenko, A., Wang, L., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.019 · Cited by 1,379 · see citing works
Self-citationExciting New Advances in Neuro-Oncology: The Avenue to a Cure for Malignant Glioma
Van Meir, E. G., Hadjipanayis, C. G., Norden, A. D., Shu, H. K., Wen, P. Y., & Olson, J. J. (2010) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20069 · Cited by 1,372 · see citing works
Self-citationMutational analysis reveals the origin and therapy-driven evolution of recurrent glioma
Johnson, B. E., Mazor, T., Hong, C., Barnes, M., Aihara, K., McLean, C. Y., Fouse, S. D., Yamamoto, S., Ueda, H., Tatsuno, K., et al. (2014) · Science · doi:10.1126/science.1239947 · Cited by 1,362 · see citing works
Tumor Self-Seeding by Circulating Cancer Cells
Kim, M.-Y., Oskarsson, T., Acharyya, S., Nguyen, D. X., Zhang, X. H.-F., Norton, L., & Massagué, J. (2009) · Cell · doi:10.1016/j.cell.2009.11.025 · Cited by 1,335 · see citing works
Allele-specific copy number analysis of tumors
Loo, P. V., Nord, S., Lingjærde, O. C., Russnes, H. G., Rye, I. H., Sun, W., Weigman, V., Marynen, P., Zetterberg, A., Naume, B., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009843107 · Cited by 1,231 · see citing works
Gerlinger, M., Horswell, S. D., Larkin, J., Rowan, A., Salm, M., Varela, I., Fisher, R. A., McGranahan, N., Matthews, N., Santos, C. R., et al. (2014) · Nature Genetics · doi:10.1038/ng.2891 · Cited by 1,211 · see citing works
Evolutionary Dynamics of Biological Games
Nowak, M. A., & Sigmund, K. (2004) · Science · doi:10.1126/science.1093411 · Cited by 1,184 · see citing works
PyClone: statistical inference of clonal population structure in cancer
Roth, A. J. L., Khattra, J. S., Yap, D., Wan, A. N. C., Laks, E., Biele, J., Ha, G., Aparicio, S. A. J. R., Bouchard‐Côté, A., & Shah, S. P. (2014) · Nature Methods · doi:10.1038/nmeth.2883 · Cited by 1,002 · see citing works
Rausch, T., Jones, D. T. W., Zapatka, M., Stütz, A. M., Zichner, T., Weischenfeldt, J., Jäger, N., Remke, M., Shih, D., Northcott, P. A., et al. (2012) · Cell · doi:10.1016/j.cell.2011.12.013 · Cited by 865 · see citing works
Sampson, J. H., Heimberger, A. B., Archer, G. E., Aldape, K., Friedman, A. H., Friedman, H. S., Gilbert, M. R., Herndon, J. E., McLendon, R. E., Mitchell, D. A., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.6963 · Cited by 808 · see citing works
荒木, 則. (2006) · Mebio oncology · Cited by 771 · see citing works
Making a tumour's bed: glioblastoma stem cells and the vascular niche
Gilbertson, R. J., & Rich, J. N. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2246 · Cited by 716 · see citing works
Mosaic Amplification of Multiple Receptor Tyrosine Kinase Genes in Glioblastoma
Snuderl, M., Fazlollahi, L., Le, L. P., Nitta, M., Zhelyazkova, B. H., Davidson, C. J., Akhavanfard, S., Cahill, D. P., Aldape, K., Betensky, R. A., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.11.005 · Cited by 708 · see citing works
Evolution of the cancer genome
Yates, L. R., & Campbell, P. J. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3317 · Cited by 645 · see citing works
Evolutionary dynamics of cancer in response to targeted combination therapy
Božić, I., Reiter, J. G., Allen, B., Tibor Antal, A., Chatterjee, K., Shah, P., Moon, Y. S., Yaqubie, A., Kelly, N. E., Le, D. T., et al. (2013) · eLife · doi:10.7554/elife.00747 · Cited by 607 · see citing works
Emerging insights into the molecular and cellular basis of glioblastomaPreprint
Dunn, G. P., Rinne, M. L., Wykosky, J., Genovese, G., Quayle, S. N., Dunn, I. F., Agarwalla, P. K., Chheda, M. G., Campos, B., Wang, A., et al. (2012) · Genes & Development · doi:10.1101/gad.187922.112 · Cited by 559 · see citing works
Self-citationSzerlip, N. J., Pedraza, A. M., Chakravarty, D., Azim, M., McGuire, J., Fang, Y., Ozawa, T., Holland, E. C., Huse, J. T., Jhanwar, S. C., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114033109 · Cited by 538 · see citing works
Self-citationMiller, C. A., White, B. S., Dees, N. D., Griffith, M., Welch, J. S., Griffith, O. L., Vij, R., Tomasson, M. H., Graubert, T. A., Walter, M. J., et al. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003665 · Cited by 444 · see citing works
Hunter, C., Smith, R., Cahill, D. P., Stephens, P., Stevens, C., Teague, J. W., Greenman, C., Edkins, S., Bignell, G. R., Davies, H. R., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0127 · Cited by 431 · see citing works
Tomasetti, C., Vogelstein, B., & Parmigiani, G. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221068110 · Cited by 414 · see citing works
MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy
Kojima, K., Konopleva, M. Y., Samudio, I. J., Shikami, M., Cabreira-Hansen, M. D. G., McQueen, T. J., Ruvolo, V. R., Tsao, T., Zeng, Z., Vassilev, L. T., et al. (2005) · Blood · doi:10.1182/blood-2005-02-0553 · Cited by 407 · see citing works
The Implications of Clonal Genome Evolution for Cancer Medicine
Aparicio, S. A. J. R., & Caldas, C. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1204892 · Cited by 350 · see citing works
<i>EGFR</i> Variant Heterogeneity in Glioblastoma Resolved through Single-Nucleus Sequencing
Francis, J. M., Zhang, C.-Z., Maire, C. L., Jung, J., Manzo, V. E., Adalsteinsson, V. A., Homer, H., Haidar, S., Blumenstiel, B., Pedamallu, C. S., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0879 · Cited by 287 · see citing works
Self-citationMetapopulation dynamics and spatial heterogeneity in cancer
González-Garcı́a, I., Solé, R. V., & Costa, J. C. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202139299 · Cited by 201 · see citing works
EXPANDS: expanding ploidy and allele frequency on nested subpopulations
Andor, N., Harness, J. V., Müller, S., Mewes, H., & Petritsch, C. K. (2013) · Bioinformatics · doi:10.1093/bioinformatics/btt622 · Cited by 138 · see citing works
Bengtsson, H. L., Wirapati, P., & Speed, T. P. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp371 · Cited by 136 · see citing works
Parent-specific copy number in paired tumor–normal studies using circular binary segmentation
Olshen, A. B., Bengtsson, H. L., Neuvial, P., Spellman, P. T., Olshen, R. A., & Seshan, V. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr329 · Cited by 122 · see citing works
Offer, H., Erez, N., Zurer, I., Tang, X., Milyavsky, M., Goldfinger, N., & Rotter, V. (2002) · Carcinogenesis · doi:10.1093/carcin/23.6.1025 · Cited by 107 · see citing works
Pant, V., Xiong, S., Jackson, J. G., Post, S. M., Abbas, H. A., Quintás‐Cardama, A., Hamir, A. N., & Lozano, G. (2013) · Genes & Development · doi:10.1101/gad.227249.113 · Cited by 83 · see citing works
Characterizing Mutational Heterogeneity in a Glioblastoma Patient with Double Recurrence
Nickel, G. C., Barnholtz‐Sloan, J. S., Gould, M. P., McMahon, S., Cohen, A. J., Adams, M. D., Guda, K., Cohen, M. L., Sloan, A. E., & LaFramboise, T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035262 · Cited by 79 · see citing works
Self-citationIshii, N., Tada, M., Hamou, M. F., et al. (1999) · Oncogene · doi:10.1038/sj.onc.1203241 · Cited by 75 · see citing works
Zheng, S., Fu, J., Vegesna, R., Mao, Y., Heathcock, L. E., Torres‐García, W., Ezhilarasan, R., Wang, S., McKenna, A., Chin, L., et al. (2013) · Genes & Development · doi:10.1101/gad.213686.113 · Cited by 73 · see citing works
Self-citationFulci, G., Ishii, N., Maurici, D., Gernert, K. M., Hainaut, P. L., Kaur, B., & Meir, E. G. V. (2002) · PubMed · Cited by 31 · see citing works
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Clonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840 · see citing works
Wen, P. Y., Weller, M., Lee, E. Q., Alexander, B. M., Barnholtz-Sloan, J. S., Barthel, F. P., Batchelor, T. T., Bindra, R. S., Chang, S. M., Chiocca, E. A., et al. (2020) · Neuro-Oncology · doi:10.1093/neuonc/noaa106 · Cited by 1,168 · see citing works
Self-citationTranscriptome analysis reveals tumor microenvironment changes in glioblastoma
Hoogstrate, Y., Draaisma, K., Ghisai, S. A., van Hijfte, L., Barin, N., de Heer, I., Coppieters, W., van den Bosch, T. P. P., Bolleboom, A., Gao, Z., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.019 · Cited by 240 · see citing works
The Many Facets of Therapy Resistance and Tumor Recurrence in Glioblastoma
Goenka, A., Tiek, D., Song, X., Huang, T., Hu, B., & Cheng, S.-Y. (2021) · Cells · doi:10.3390/cells10030484 · Cited by 169 · see citing works
Myc-Driven glycolysis is a therapeutic target in glioblastoma
Tateishi, K., Iafrate, A. J., Ho, Q., Curry, W. T., Batchelor, T. T., Flaherty, K. T., Onozato, M. L., Lelic, N., Sundaram, S., Cahill, D. P., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2274 · Cited by 160 · see citing works
Habashy, K. J., Mansour, R., Moussalem, C., Sawaya, R., & Massaad, M. J. (2022) · British Journal of Cancer · doi:10.1038/s41416-022-01864-w · Cited by 95 · see citing works
Wang, B., Peng, F., Huang, W., Zhou, J., Zhang, N., Sheng, J., Haruehanroengra, P., He, G., & Han, B. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.12.013 · Cited by 73 · see citing works
Malta, T. M., Sabedot, T. S., Morosini, N. S., Datta, I., Garofano, L., Vallentgoed, W., Varn, F. S., Aldape, K., D'Angelo, F., Bakas, S., et al. (2024) · Cancer Research · doi:10.1158/0008-5472.can-23-2093 · Cited by 68 · see citing works
Self-citation
- Authors
- Kim, H., Zheng, S., Amini, S. S., Virk, S. M., Mikkelsen, T., Brat, D. J., Grimsby, J., Sougnez, C., Muller, F., Hu, J., Sloan, A. E., Cohen, M. L., Van Meir, E. G., Scarpace, L., Laird, P. W., Weinstein, J. N., Lander, E. S., Gabriel, S., Getz, G., Meyerson, M., Chin, L., Barnholtz-Sloan, J. S., & Verhaak, R. G. W.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Case Comprehensive Cancer Center (US)
- Henry Ford Hospital (US)
- Emory University (US)
- Broad Institute (US)
- University Hospitals Cleveland Medical Center (US)
- Van Andel Institute (US)
- Corresponding author
- Verhaak, Roel G.W.
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2015-02-03
- Volume
- 25
- Issue
- 3
- Pages
- 316-327
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC4352879
- OpenAlex
- W2129418270
- Cited by
- 411
- References
- 56
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 27 · 2023: 52 · 2022: 41 · 2021: 42 · 2020: 37 · 2019: 42 · 2018: 45 · 2017: 36 · 2016: 33 · 2015: 10 · 2014: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- NCI (P50 CA127001, P50 CA083639-12, P01 CA085878, R01 CA190121, CA016672)
- CPRIT (R140606)
- MD Anderson Genome Data Analysis Center (CA143883)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- glioblastoma, tumor recurrence, tumor evolution, subclonal heterogeneity, residual tumor cells, treatment resistance, p53 pathway, cancer stem cells, clonal evolution, tumor heterogeneity
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Brain Neoplasms, Glioblastoma, Humans, Middle Aged, Mutation, Neoplasm Recurrence, Local, Signal Transduction, Genome, Human, Tumor Suppressor Protein p53, Treatment Outcome, DNA Methylation, Polymorphism, Single Nucleotide, Genomics, Young Adult, DNA Copy Number Variations, High-Throughput Nucleotide Sequencing, Exome, Mutation Rate, Neoplasm Grading, Clonal Evolution
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