Melanoma genome sequencing reveals frequent PREX2 mutations
Open accessAbstract
Whole-genome sequencing of 25 metastatic melanomas and matched germline DNA in humans reveals that the highest mutation load is associated with chronic sun exposure, and that the PREX2 gene is mutated in approximately 14 per cent of cases Melanoma is a highly metastatic cancer, characterized by high lethality and rapid development of resistance to treatment. Whole-genome sequencing of 25 metastatic melanomas and matched germline DNA reveals that the mutation rate varies widely, with the highest mutation load associated with chronic exposure to sunlight. PREX2 — a PTEN-interacting protein previously implicated in breast cancer — is mutated in approximately 14% of cases. Although the precise role of PREX2 in melanoma remains to be elucidated, ectopic expression of its mutant form accelerates tumour formation of immortalized human melanocytes in vivo. Melanoma is notable for its metastatic propensity, lethality in the advanced setting and association with ultraviolet exposure early in life1. To obtain a comprehensive genomic view of melanoma in humans, we sequenced the genomes of 25 metastatic melanomas and matched germline DNA. A wide range of point mutation rates was observed: lowest in melanomas whose primaries arose on non-ultraviolet-exposed hairless skin of the extremities (3 and 14 per megabase (Mb) of genome), intermediate in those originating from hair-bearing skin of the trunk (5–55 per Mb), and highest in a patient with a documented history of chronic sun exposure (111 per Mb). Analysis of whole-genome sequence data identified PREX2 (phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2)—a PTEN-interacting protein and negative regulator of PTEN in breast cancer2—as a significantly mutated gene with a mutation frequency of approximately 14% in an independent extension cohort of 107 human melanomas. PREX2 mutations are biologically relevant, as ectopic expression of mutant PREX2 accelerated tumour formation of immortalized human melanocytes in vivo. Thus, whole-genome sequencing of human melanoma tumours revealed genomic evidence of ultraviolet pathogenesis and discovered a new recurrently mutated gene in melanoma.
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Multiple genome-wide sequencing studies have revealed a paucity of NER gene defects in sporadic malignant melanoma within the general population.
“In view of this, it may be surprising that multiple genome-wide sequencing studies have revealed a paucity of NER gene defects in sporadic MM within the general population (2, 6, 7).”
From A genome-wide screen reveals that Dyrk1A kinase promotes nucleotide excision repair by preventing aberrant overexpression of cyclin D1 and p21 (2023) · cites this paper as [7]
The paper’s Abstract (page unavailable) describes whole-genome sequencing of 25 metastatic melanomas and reports mutation patterns, but it does not assess whether NER gene defects are rare. Searches for NER, nucleotide excision repair, and DNA repair gene defects found no passage supporting the attributed finding. (LLM, conf=0.72)
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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
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
Self-citationInhibition of Mutated, Activated BRAF in Metastatic Melanoma
Flaherty, K. T., Puzanov, I. J., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. A., O'Dwyer, P. J., Lee, R. J., Grippo, J. F., Nolop, K. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002011 · Cited by 3,542 · see citing works
Patterns of somatic mutation in human cancer genomes
Greenman, C. D., Stephens, P., Smith, R., Dalgliesh, G. L., Hunter, C., Bignell, G. R., Davies, H. R., Teague, J. W., Butler, A. P., Stevens, C., et al. (2007) · Nature · doi:10.1038/nature05610 · Cited by 3,062 · see citing works
Distinct Sets of Genetic Alterations in Melanoma
Curtin, J. A., Fridlyand, J., Kageshita, T., Patel, H. N., Busam, K. J., Kutzner, H., Cho, K.-H., Aiba, S., Bröcker, E.-B., LeBoit, P. E., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050092 · Cited by 2,747 · see citing works
Massive genomic rearrangement acquired in a single catastrophic event during cancer development
Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., et al. (2011) · Cell · doi:10.1016/j.cell.2010.11.055 · Cited by 2,414 · see citing works
Predicting the functional impact of protein mutations: application to cancer genomics
Reva, B. A., Antipin, Y., & Sander, C. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr407 · Cited by 1,987 · see citing works
A comprehensive catalogue of somatic mutations from a human cancer genome
Pleasance, E. D., Cheetham, R. K., Stephens, P. J., McBride, D. J., Humphray, S. J., Greenman, C. D., Varela, I., Lin, M.-L., Ordóñez, G. R., Bignell, G. R., et al. (2010) · Nature · doi:10.1038/nature08658 · Cited by 1,696 · see citing works
Self-citationSomatic Activation of KIT in Distinct Subtypes of Melanoma
Curtin, J. A., BUSAM, K. J., Pinkel, D., & Bastian, B. C. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.2984 · Cited by 1,612 · see citing works
Garraway, L. A., Widlund, H. R., Rubin, M. A., Getz, G., Berger, A. J., Ramaswamy, S., Beroukhim, R., Milner, D. A., Granter, S. R., Du, J., et al. (2005) · Nature · doi:10.1038/nature03664 · Cited by 1,548 · see citing works
Self-citationInitial genome sequencing and analysis of multiple myeloma
Chapman, M. A., Lawrence, M. S., Keats, J. J., Cibulskis, K., Sougnez, C. L., Schinzel, A. C., Harview, C. L., Brunet, J.-P., Ahmann, G. J., Adli, M., et al. (2011) · Nature · doi:10.1038/nature09837 · Cited by 1,422 · see citing works
Self-citationThe genomic complexity of primary human prostate cancer
Berger, M. F., Lawrence, M. S., Demichelis, F., Drier, Y., Cibulskis, K., Sivachenko, A., Sboner, A., Esgueva, R., Pflueger, D., Sougnez, C. L., et al. (2011) · Nature · doi:10.1038/nature09744 · Cited by 1,213 · see citing works
Self-citationDiverse somatic mutation patterns and pathway alterations in human cancers
Kan, Z., Jaiswal, B. S., Stinson, J., Janakiraman, V., Bhatt, D., Stern, H. M., Yue, P., Haverty, P. M., Bourgon, R., Zheng, J., et al. (2010) · Nature · doi:10.1038/nature09208 · Cited by 1,018 · 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
Signatures of mutation and selection in the cancer genome
Bignell, G. R., Greenman, C. D., Davies, H., Butler, A. P., Edkins, S., Andrews, J. M., Buck, G., Chen, L., Beare, D., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08768 · Cited by 707 · see citing works
Forbes, S. A., Tang, G., Bindal, N., Bamford, S., Dawson, E., Cole, C. G., Kok, C. Y., Jia, M., Ewing, R., Menzies, A. H., et al. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp995 · Cited by 572 · see citing works
Exome sequencing identifies GRIN2A as frequently mutated in melanoma
Program, N. C. S., Wei, X., Walia, V., Lin, J., Teer, J. K., Prickett, T. D., Gartner, J. J., Davis, S. R., Stemke‐Hale, K., Davies, M. A., et al. (2011) · Nature Genetics · doi:10.1038/ng.810 · Cited by 463 · see citing works
Major Response to Imatinib Mesylate in KIT-Mutated Melanoma
Hodi, F. S., Friedlander, P. A., Corless, C. L., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.14.0707 · Cited by 419 · see citing works
Integrative analysis of the melanoma transcriptome
Berger, M. F., Levin, J. Z., Vijayendran, K., Sivachenko, A., Adiconis, X., Maguire, J., Johnson, L. A., Robinson, J., Verhaak, R. G., Sougnez, C., et al. (2010) · Genome Research · doi:10.1101/gr.103697.109 · Cited by 305 · see citing works
Self-citationThe genetics of malignant melanoma: lessons from mouse and man
Chin, L. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1145 · Cited by 300 · see citing works
Self-citationResistance to BRAF Inhibition in Melanomas
Solit, D. B., & Rosen, N. X. (2011) · New England Journal of Medicine · doi:10.1056/nejmcibr1013704 · Cited by 243 · see citing works
Activation of the PI3K Pathway in Cancer Through Inhibition of PTEN by Exchange Factor P-REX2a
Fine, B. M., Hodakoski, C., Koujak, S., Su, T., Saal, L. H., Maurer, M., Hopkins, B. D., Keniry, M. E., Sulis, M. L., Mense, S. M., et al. (2009) · Science · doi:10.1126/science.1173569 · Cited by 238 · see citing works
The specificity of UV-induced mutations at an endogenous locus in mammalian cells.
Drobetsky, E. A., Grosovsky, A. J., & Glickman, B. W. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.24.9103 · Cited by 211 · see citing works
Kloosterman, W. P., Hoogstraat, M., Paling, O., Tavakoli-Yaraki, M., Renkens, I., Vermaat, J. S., van Roosmalen, M. J., van Lieshout, S., Nijman, I. J., Roessingh, W., et al. (2011) · Genome Biology · doi:10.1186/gb-2011-12-10-r103 · Cited by 204 · see citing works
Nakahata, S. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki338 · Cited by 184 · see citing works
An Oncogenic Role for <i>ETV1</i> in Melanoma
Jané-Valbuena, J., Widlund, H. R., Perner, S., Johnson, L. A., Dibner, A. C., Lin, W. M., Baker, A. C., Nazarian, R. M., Vijayendran, K. G., Sellers, W. R., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3092 · Cited by 115 · see citing works
Self-citationMutation-driven drug development in melanoma
Flaherty, K. T., Hodi, F. S., & Bastian, B. C. (2010) · Current Opinion in Oncology · doi:10.1097/cco.0b013e32833888ee · Cited by 101 · see citing works
Strand specificity for UV-induced DNA repair and mutations in the Chinese hamster HPRT gene
Vrieling, H., Venema, J., van Rooyen, M. L., van Hoffen, A., Menichini, P., Zdzienicka, M. Z., Simons, J. W. I. M., Mullenders, L. H. F., & van Zeeland, A. A. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.9.2411 · Cited by 96 · see citing works
Mutation patterns in cancer genomes
Rubin, A. F., & Green, P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912499106 · Cited by 80 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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-citationPD-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
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-citationGenetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J. M., Desrichard, A., Walsh, L. A., Postow, M. A., Wong, P., Ho, T. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1406498 · Cited by 4,286 · see citing works
Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden
Chalmers, Z. R., Connelly, C. F., Fabrizio, D., Gay, L., Ali, S. M., Ennis, R., Schrock, A., Campbell, B., Shlien, A., Chmielecki, J., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0424-2 · Cited by 3,519 · see citing works
Self-citationGenomic classification of cutaneous melanoma
Akbani, R., Akdemir, K. C., Aksoy, B. A., Albert, M., Ally, A., Amin, S. B., Arachchi, H., Arora, A., Auman, J. T., Ayala, B., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.044 · Cited by 3,151 · see citing works
Self-citationWhole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642 · 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
Self-citationIntegrated genomic characterization of pancreatic ductal adenocarcinoma
Raphael, B. J., Hruban, R. H., Aguirre, A. J., Moffitt, R. A., Yeh, J. J., Stewart, C., Robertson, A. G., Cherniack, A. D., Gupta, M., Getz, G., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.007 · Cited by 2,019 · see citing works
Self-citationHighly 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
Self-citationMapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing
Imielinski, M., Berger, A. H., Hammerman, P. S., Hernandez, B., Pugh, T. J., Hodis, E., Cho, J., Suh, J., Capelletti, M., Sivachenko, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.029 · Cited by 1,789 · see citing works
Self-citationExome 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
Resistance to checkpoint blockade therapy through inactivation of antigen presentation
Sade-Feldman, M., Jiao, Y. J., Chen, J. H., Rooney, M. S., Barzily-Rokni, M., Eliane, J.-P., Bjorgaard, S. L., Hammond, M. R., Vitzthum, H., Blackmon, S. M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01062-w · Cited by 1,005 · see citing works
Self-citationCell-of-origin chromatin organization shapes the mutational landscape of cancer
Polak, P., Karlić, R., Koren, A., Thurman, R., Sandstrom, R., Lawrence, M. S., Reynolds, A., Rynes, E., Vlahoviček, K., Stamatoyannopoulos, J. A., et al. (2015) · Nature · doi:10.1038/nature14221 · Cited by 557 · see citing works
Self-citationMelanoma: from mutations to medicine
Tsao, H., Chin, L., Garraway, L. A., & Fisher, D. E. (2012) · Genes & Development · doi:10.1101/gad.191999.112 · Cited by 496 · see citing works
Self-citationMutational signatures: the patterns of somatic mutations hidden in cancer genomes
Alexandrov, L. B., & Stratton, M. R. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.11.014 · Cited by 488 · see citing works
Cook, D. R., Rossman, K. L., & Der, C. J. (2014) · Oncogene · doi:10.1038/onc.2013.362 · Cited by 378 · see citing works
Multifaceted pathways protect human skin from UV radiation
Natarajan, V. T., Ganju, P., Ramkumar, A., Grover, R., & Gokhale, R. S. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1548 · Cited by 244 · see citing works
RAS: Striking at the Core of the Oncogenic Circuitry
Gimple, R. C., & Wang, X. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00965 · Cited by 174 · see citing works
Lucas, R. M., Norval, M., Neale, R. E., Young, A. R., de Gruijl, F. R., Takizawa, Y., & van der Leun, J. C. (2014) · Photochemical & Photobiological Sciences · doi:10.1039/c4pp90033b · Cited by 158 · see citing works
Roles of UVA radiation and DNA damage responses in melanoma pathogenesis
Khan, A. Q., Travers, J. B., & Kemp, M. G. (2018) · Environmental and Molecular Mutagenesis · doi:10.1002/em.22176 · Cited by 152 · see citing works
UV-Induced Molecular Signaling Differences in Melanoma and Non-melanoma Skin Cancer
Liu-Smith, F., Jia, J., & Zheng, Y. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-56017-5_3 · Cited by 147 · see citing works
Germline MC1R status influences somatic mutation burden in melanoma
Robles-Espinoza, C. D., Roberts, N. D., Chen, S., Leacy, F. P., Alexandrov, L. B., Pornputtapong, N., Halaban, R., Krauthammer, M., Cui, R., Timothy Bishop, D., et al. (2016) · Nature Communications · doi:10.1038/ncomms12064 · Cited by 124 · see citing works
Understanding mutagenesis through delineation of mutational signatures in human cancer
Petljak, M., & Alexandrov, L. B. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw055 · Cited by 110 · see citing works
Xia, J., Jia, P., Hutchinson, K. E., Dahlman, K. B., Johnson, D., Sosman, J., Pao, W., & Zhao, Z. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0804 · Cited by 94 · see citing works
The genetics of melanoma: recent advances
Hill, V. K., Gartner, J. J., Samuels, Y., & Goldstein, A. M. (2013) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153429 · Cited by 86 · see citing works
Rebecca, V. W., Massaro, R. R., Fedorenko, I. V., Sondak, V. K., Anderson, A. R. A., Kim, E., Amaravadi, R. K., Maria‐Engler, S. S., Messina, J. L., Gibney, G. T., et al. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12227 · Cited by 58 · see citing works
“It is already known from extensive studies in cell lines harboring BRAF mutations that melanoma survival is dependent upon the MAPK pathway, which exerts its effects in part through regulation of the pro-apoptotic proteins BIM and BMF (Boisvert-Adamo and Aplin, 2008; Cartlidge et al., 2008).”
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Bacolla, A., Temiz, N. A., Yi, M., Ivanic, J., Cer, R. Z., Donohue, D. E., Ball, E. V., Mudunuri, U. S., Wang, G., Jain, A., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003816 · Cited by 40 · see citing works
Can cancer researchers accurately judge whether preclinical reports will reproduce?
Benjamin, D., Mandel, D. R., & Kimmelman, J. (2017) · PLOS Biology · doi:10.1371/journal.pbio.2002212 · Cited by 32 · see citing works
Bélanger, F., Rajotte, V., & Drobetsky, E. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085294 · Cited by 29 · see citing works
Genome-wide methylated CpG island profiles of melanoma cells reveal a melanoma coregulation network
Li, J.-L., Mazar, J., Zhong, C., Faulkner, G. J., Govindarajan, S. S., Zhang, Z., Dinger, M. E., Meredith, G., Adams, C., Zhang, S., et al. (2013) · Scientific Reports · doi:10.1038/srep02962 · Cited by 21 · see citing works
Bélanger, F., Roussel, C., Sawchyn, C., St-Hilaire, E., Gezzar-Dandashi, S., Kimenyi Ishimwe, A. B., Mallette, F. A., Wurtele, H., & Drobetsky, E. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104900 · Cited by 9 · see citing works
- Authors
- Berger, M. F., Hodis, E., Heffernan, T. P., Deribe, Y. L., Lawrence, M. S., Protopopov, A., Ivanova, E., Watson, I. R., Nickerson, E., Ghosh, P., Zhang, H., Zeid, R., Ren, X., Cibulskis, K., Sivachenko, A. Y., Wagle, N., Sucker, A., Sougnez, C., Onofrio, R., Ambrogio, L., Auclair, D., Fennell, T., Carter, S. L., Drier, Y., Stojanov, P., Singer, M. A., Voet, D., Jing, R., Saksena, G., Barretina, J., Ramos, A. H., Pugh, T. J., Stransky, N., Parkin, M., Winckler, W., Mahan, S., Ardlie, K., Baldwin, J., Wargo, J., Schadendorf, D., Meyerson, M., Gabriel, S. B., Golub, T. R., Wagner, S. N., Lander, E. S., Getz, G., Chin, L., & Garraway, L. A.
- Affiliations
- Broad Institute (US)
- Dana-Farber Cancer Institute (US)
- Harvard University (US)
- Essen University Hospital (DE)
- Weizmann Institute of Science (IL)
- Massachusetts General Hospital (US)
- Austrian Academy of Sciences (AT)
- Corresponding author
- Chin, Lynda
- Garraway, Levi A.
- ORCID
- Berger, Michael F.
- Hodis, Eran
- Heffernan, Timothy P.
- Lawrence, Michael S.
- Protopopov, Alexei
- Ivanova, Elena
- Watson, Ian R.
- Zhang, Hailei
- Cibulskis, Kristian
- Sivachenko, Andrey Y.
- Wagle, Nikhil
- Sucker, Antje
- Auclair, Daniel
- Carter, Scott L.
- Drier, Yotam
- Jing, Rui
- Saksena, Gordon
- Barretina, Jordi
- Pugh, Trevor J.
- Stransky, Nicolas
- Winckler, Wendy
- Ardlie, Kristin
- Wargo, Jennifer
- Schadendorf, Dirk
- Meyerson, Matthew
- Gabriel, Stacey B.
- Golub, Todd R.
- Wagner, Stephan N.
- Lander, Eric S.
- Getz, Gad
- Garraway, Levi A.
- Venue
- Nature
- Published
- 2012-05
- Volume
- 485
- Issue
- 7399
- Pages
- 502-506
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3367798
- OpenAlex
- W2149793889
- Semantic Scholar
- 6ed846842b065a52cbcceab92929afc2946aa3ef
- Cited by
- 756
- References
- 29
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 29 · 2023: 35 · 2022: 39 · 2021: 43 · 2020: 25 · 2019: 47 · 2018: 43 · 2017: 73 · 2016: 73 · 2015: 89 · 2014: 85 · 2013: 107 · 2012: 39
- FWCI
- 41.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- Howard Hughes Medical Institute
- Melanoma Research Alliance
- Dana-Farber Cancer Institute
- Wellcome Trust
- Broad Institute
- Austrian Science Fund
- National Institutes of Health (DP2OD002750)
- National Human Genome Research Institute (U54HG003067)
- National Cancer Institute (R33CA155554, R33CA126674, T32CA009172)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- melanoma, metastatic melanoma, UV exposure, chronic sun exposure, mutation rate, germline DNA, PTEN, tumor suppressor, recurrent mutations, skin cancer pathogenesis
- MeSH terms
- DNA Damage, DNA Mutational Analysis, Humans, Melanocytes, Melanoma, Mutation, Oncogenes, Sunlight, Ultraviolet Rays, Genome, Human, Gene Expression Regulation, Neoplastic, Mutagenesis, Guanine Nucleotide Exchange Factors, Chromosome Breakpoints
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 ›
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