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Cell. 2015 Jun 18;161(7):1681-96. doi: 10.1016/j.cell.2015.05.044.

Genomic Classification of Cutaneous Melanoma.

Collaborators (352)

Akbani R, Akdemir KC, Aksoy BA, Albert M, Ally A, Amin SB, Arachchi H, Arora A, Auman JT, Ayala B, Baboud J, Balasundaram M, Balu S, Barnabas N, Bartlett J, Bartlett P, Bastian BC, Baylin SB, Behera M, Belyaev D, Benz C, Bernard B, Beroukhim R, Bir N, Black AD, Bodenheimer T, Boice L, Boland GM, Bono R, Bootwalla MS, Bosenberg M, Bowen J, Bowlby R, Bristow CA, Brockway-Lunardi L, Brooks D, Brzezinski J, Bshara W, Buda E, Burns WR, Butterfield YS, Button M, Calderone T, Cappellini GA, Carter C, Carter SL, Cherney L, Cherniack AD, Chevalier A, Chin L, Cho J, Cho RJ, Choi YL, Chu A, Chudamani S, Cibulskis K, Ciriello G, Clarke A, Coons S, Cope L, Crain D, Curley E, Danilova L, D'Atri S, Davidsen T, Davies MA, Delman KA, Demchok JA, Deng QA, Deribe YL, Dhalla N, Dhir R, DiCara D, Dinikin M, Dubina M, Ebrom JS, Egea S, Eley G, Engel J, Eschbacher JM, Fedosenko KV, Felau I, Fennell T, Ferguson ML, Fisher S, Flaherty KT, Frazer S, Frick J, Fulidou V, Gabriel SB, Gao J, Gardner J, Garraway LA, Gastier-Foster JM, Gaudioso C, Gehlenborg N, Genovese G, Gerken M, Gershenwald JE, Getz G, Gomez-Fernandez C, Gribbin T, Grimsby J, Gross B, Guin R, Gutschner T, Hadjipanayis A, Halaban R, Hanf B, Haussler D, Haydu LE, Hayes DN, Hayward NK, Heiman DI, Herbert L, Herman JG, Hersey P, Hoadley KA, Hodis E, Holt RA, Hoon DS, Hoppough S, Hoyle AP, Huang FW, Huang M, Huang S, Hutter CM, Ibbs M, Iype L, Jacobsen A, Jakrot V, Janning A, Jeck WR, Jefferys SR, Jensen MA, Jones CD, Jones SJ, Ju Z, Kakavand H, Kang H, Kefford RF, Khuri FR, Kim J, Kirkwood JM, Klode J, Korkut A, Korski K, Krauthammer M, Kucherlapati R, Kwong LN, Kycler W, Ladanyi M, Lai PH, Laird PW, Lander E, Lawrence MS, Lazar AJ, Łaźniak R, Lee D, Lee JE, Lee J, Lee K, Lee S, Lee W, Leporowska E, Leraas KM, Li HI, Lichtenberg TM, Lichtenstein L, Lin P, Ling S, Liu J, Liu O, Liu W, Long GV, Lu Y, Ma S, Ma Y, Mackiewicz A, Mahadeshwar HS, Malke J, Mallery D, Manikhas GM, Mann GJ, Marra MA, Matejka B, Mayo M, Mehrabi S, Meng S, Meyerson M, Mieczkowski PA, Miller JP, Miller ML, Mills GB, Moiseenko F, Moore RA, Morris S, Morrison C, Morton D, Moschos S, Mose LE, Muller FL, Mungall AJ, Murawa D, Murawa P, Murray BA, Nezi L, Ng S, Nicholson D, Noble MS, Osunkoya A, Owonikoko TK, Ozenberger BA, Pagani E, Paklina OV, Pantazi A, Parfenov M, Parfitt J, Park PJ, Park WY, Parker JS, Passarelli F, Penny R, Perou CM, Pihl TD, Potapova O, Prieto VG, Protopopov A, Quinn MJ, Radenbaugh A, Rai K, Ramalingam SS, Raman AT, Ramirez NC, Ramirez R, Rao U, Rathmell WK, Ren X, Reynolds SM, Roach J, Robertson AG, Ross MI, Roszik J, Russo G, Saksena G, Saller C, Samuels Y, Sander C, Sander C, Sandusky G, Santoso N, Saul M, Saw RP, Schadendorf D, Schein JE, Schultz N, Schumacher SE, Schwallier C, Scolyer RA, Seidman J, Sekhar PC, Sekhon HS, Senbabaoglu Y, Seth S, Shannon KF, Sharpe S, Sharpless NE, Shaw KR, Shelton C, Shelton T, Shen R, Sheth M, Shi Y, Shiau CJ, Shmulevich I, Sica GL, Simons JV, Sinha R, Sipahimalani P, Sofia HJ, Soloway MG, Song X, Sougnez C, Spillane AJ, Spychała A, Stretch JR, Stuart J, Suchorska WM, Sucker A, Sumer SO, Sun Y, Synott M, Tabak B, Tabler TR, Tam A, Tan D, Tang J, Tarnuzzer R, Tarvin K, Tatka H, Taylor BS, Teresiak M, Thiessen N, Thompson JF, Thorne L, Thorsson V, Trent JM, Triche TJ Jr, Tsai KY, Tsou P, Van Den Berg DJ, Van Allen EM, Veluvolu U, Verhaak RG, Voet D, Voronina O, Walter V, Walton JS, Wan Y, Wang Y, Wang Z, Waring S, Watson IR, Weinhold N, Weinstein JN, Weisenberger DJ, White P, Wilkerson MD, Wilmott JS, Wise L, Wiznerowicz M, Woodman SE, Wu CJ, Wu CC, Wu J, Wu Y, Xi R, Xu AW, Yang D, Yang L, Yang L, Zack TI, Zenklusen JC, Zhang H, Zhang J, Zhang W, Zhao X, Zhu J, Zhu K, Zimmer L, Zmuda E, Zou L.

Abstract

We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.

PMID:
26091043
PMCID:
PMC4580370
DOI:
10.1016/j.cell.2015.05.044
[Indexed for MEDLINE]
Free PMC Article
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