Genomic Classification of Cutaneous Melanoma

Rehan Akbani; Kadir C. Akdemir; B. Arman Aksoy; Monique Albert; Adrian Ally; Samirkumar B. Amin; Harindra Arachchi; Arshi Arora; J. Todd Auman; Brenda Ayala; Julien Baboud; Miruna Balasundaram; Saianand Balu; Nandita Barnabas; John Bartlett; Pam Bartlett; Boris C. Bastian; Stephen B. Baylin; Madhusmita Behera; Dmitry Belyaev; Christopher Benz; Brady Bernard; Rameen Beroukhim; Natalie Bir; Aaron D. Black; Tom Bodenheimer; Lori Boice; Genevieve M. Boland; Riccardo Bono; Moiz S. Bootwalla; Marcus Bosenberg; Jay Bowen; Reanne Bowlby; Christopher A. Bristow; Laura Brockway-Lunardi; Denise Brooks; Jakub Brzezinski; Wiam Bshara; Elizabeth Buda; William R. Burns; Yaron S.N. Butterfield; Michael Button; Tiffany Calderone; Giancarlo Antonini Cappellini; Candace Carter; Scott L. Carter; Lynn Cherney; Andrew D. Cherniack; Aaron Chevalier; Lynda Chin; Juok Cho; Raymond J. Cho; Yoon La Choi; Andy Chu; Sudha Chudamani; Kristian Cibulskis; Giovanni Ciriello; Amanda Clarke; Stephen Coons; Leslie Cope; Daniel Crain; Erin Curley; Ludmila Danilova; Stefania D'Atri; Tanja Davidsen; Michael A. Davies; Keith A. Delman; John A. Demchok; Qixia A. Deng; Yonathan Lissanu Deribe; Noreen Dhalla; Rajiv Dhir; Daniel Dicara; Michael Dinikin; Michael Dubina; J. Stephen Ebrom; Sophie Egea; Greg Eley; Jay Engel; Jennifer M. Eschbacher; Konstantin V. Fedosenko; Ina Felau; Timothy Fennell; Martin L. Ferguson; Sheila Fisher; Keith T. Flaherty; Scott Frazer; Jessica Frick; Victoria Fulidou; Stacey B. Gabriel; Jianjiong Gao; Johanna Gardner; Levi A. Garraway; Julie M. Gastier-Foster; Carmelo Gaudioso; Nils Gehlenborg; Giannicola Genovese; Mark Gerken; Jeffrey E. Gershenwald; Gad Getz; Carmen Gomez-Fernandez; Thomas Gribbin; Jonna Grimsby; Benjamin Gross; Ranabir Guin; Tony Gutschner; Angela Hadjipanayis; Ruth Halaban; Benjamin Hanf; David Haussler; Lauren E. Haydu; D. Neil Hayes; Nicholas K. Hayward; David I. Heiman; Lynn Herbert; James G. Herman; Peter Hersey; Katherine A. Hoadley; Eran Hodis; Robert A. Holt; Dave Sb Hoon; Susan Hoppough; Alan P. Hoyle; Franklin W. Huang; Mei Huang; Sharon Huang; Carolyn M. Hutter; Matthew Ibbs; Lisa Iype; Anders Jacobsen; Valerie Jakrot; Alyssa Janning; William R. Jeck; Stuart R. Jefferys; Mark A. Jensen; Corbin D. Jones; Steven J.M. Jones; Zhenlin Ju; Hojabr Kakavand; Hyojin Kang; Richard F. Kefford; Fadlo R. Khuri; Jaegil Kim; John M. Kirkwood; Joachim Klode; Anil Korkut; Konstanty Korski; Michael Krauthammer; Raju Kucherlapati; Lawrence N. Kwong; Witold Kycler; Marc Ladanyi; Phillip H. Lai; Peter W. Laird; Eric Lander; Michael S. Lawrence; Alexander J. Lazar; Radoslaw Łaźniak; Darlene Lee; Jeffrey E. Lee; Junehawk Lee; Kenneth Lee; Semin Lee; William Lee; Ewa Leporowska; Kristen M. Leraas; Haiyan I. Li; Tara M. Lichtenberg; Lee Lichtenstein; Pei Lin; Shiyun Ling; Jia Liu; Ouida Liu; Wenbin Liu; Georgina V. Long; Yiling Lu; Singer Ma; Yussanne Ma; Andrzej Mackiewicz; Harshad S. Mahadeshwar; Jared Malke; David Mallery; Georgy M. Manikhas; Graham J. Mann; Marco A. Marra; Brenna Matejka; Michael Mayo; Sousan Mehrabi; Shaowu Meng; Matthew Meyerson; Piotr A. Mieczkowski; John P. Miller; Martin L. Miller; Gordon B. Mills; Fedor Moiseenko; Richard A. Moore; Scott Morris; Carl Morrison; Donald Morton; Stergios Moschos; Lisle E. Mose; Florian L. Muller; Andrew J. Mungall; Dawid Murawa; Pawel Murawa; Bradley A. Murray; Luigi Nezi; Sam Ng; Dana Nicholson; Michael S. Noble; Adeboye Osunkoya; Taofeek K. Owonikoko; Bradley A. Ozenberger; Elena Pagani; Oxana V. Paklina; Angeliki Pantazi; Michael Parfenov; Jeremy Parfitt; Peter J. Park; Woong Yang Park; Joel S. Parker; Francesca Passarelli; Robert Penny; Charles M. Perou; Todd D. Pihl; Olga Potapova; Victor G. Prieto; Alexei Protopopov; Michael J. Quinn; Amie Radenbaugh; Kunal Rai; Suresh S. Ramalingam; Ayush T. Raman; Nilsa C. Ramirez; Ricardo Ramirez; Uma Rao; W. Kimryn Rathmell; Xiaojia Ren; Sheila M. Reynolds; Jeffrey Roach; A. Gordon Robertson; Merrick I. Ross; Jason Roszik; Giandomenico Russo; Gordon Saksena; Charles Saller; Yardena Samuels; Chris Sander; Cindy Sander; George Sandusky; The Cancer Genome Atlas Network

doi:10.1016/j.cell.2015.05.044

Genomic Classification of Cutaneous Melanoma

Rehan Akbani, Kadir C. Akdemir, B. Arman Aksoy, Monique Albert, Adrian Ally, Samirkumar B. Amin, Harindra Arachchi, Arshi Arora, J. Todd Auman, Brenda Ayala, Julien Baboud, Miruna Balasundaram, Saianand Balu, Nandita Barnabas, John Bartlett, Pam Bartlett, Boris C. Bastian, Stephen B. Baylin, Madhusmita Behera, Dmitry BelyaevChristopher Benz, Brady Bernard, Rameen Beroukhim, Natalie Bir, Aaron D. Black, Tom Bodenheimer, Lori Boice, Genevieve M. Boland, Riccardo Bono, Moiz S. Bootwalla, Marcus Bosenberg, Jay Bowen, Reanne Bowlby, Christopher A. Bristow, Laura Brockway-Lunardi, Denise Brooks, Jakub Brzezinski, Wiam Bshara, Elizabeth Buda, William R. Burns, Yaron S.N. Butterfield, Michael Button, Tiffany Calderone, Giancarlo Antonini Cappellini, Candace Carter, Scott L. Carter, Lynn Cherney, Andrew D. Cherniack, Aaron Chevalier, Lynda Chin, Juok Cho, Raymond J. Cho, Yoon La Choi, Andy Chu, Sudha Chudamani, Kristian Cibulskis, Giovanni Ciriello, Amanda Clarke, Stephen Coons, Leslie Cope, Daniel Crain, Erin Curley, Ludmila Danilova, Stefania D'Atri, Tanja Davidsen, Michael A. Davies, Keith A. Delman, John A. Demchok, Qixia A. Deng, Yonathan Lissanu Deribe, Noreen Dhalla, Rajiv Dhir, Daniel Dicara, Michael Dinikin, Michael Dubina, J. Stephen Ebrom, Sophie Egea, Greg Eley, Jay Engel, Jennifer M. Eschbacher, Konstantin V. Fedosenko, Ina Felau, Timothy Fennell, Martin L. Ferguson, Sheila Fisher, Keith T. Flaherty, Scott Frazer, Jessica Frick, Victoria Fulidou, Stacey B. Gabriel, Jianjiong Gao, Johanna Gardner, Levi A. Garraway, Julie M. Gastier-Foster, Carmelo Gaudioso, Nils Gehlenborg, Giannicola Genovese, Mark Gerken, Jeffrey E. Gershenwald, Gad Getz, Carmen Gomez-Fernandez, Thomas Gribbin, Jonna Grimsby, Benjamin Gross, Ranabir Guin, Tony Gutschner, Angela Hadjipanayis, Ruth Halaban, Benjamin Hanf, David Haussler, Lauren E. Haydu, D. Neil Hayes, Nicholas K. Hayward, David I. Heiman, Lynn Herbert, James G. Herman, Peter Hersey, Katherine A. Hoadley, Eran Hodis, Robert A. Holt, Dave Sb Hoon, Susan Hoppough, Alan P. Hoyle, Franklin W. Huang, Mei Huang, Sharon Huang, Carolyn M. Hutter, Matthew Ibbs, Lisa Iype, Anders Jacobsen, Valerie Jakrot, Alyssa Janning, William R. Jeck, Stuart R. Jefferys, Mark A. Jensen, Corbin D. Jones, Steven J.M. Jones, Zhenlin Ju, Hojabr Kakavand, Hyojin Kang, Richard F. Kefford, Fadlo R. Khuri, Jaegil Kim, John M. Kirkwood, Joachim Klode, Anil Korkut, Konstanty Korski, Michael Krauthammer, Raju Kucherlapati, Lawrence N. Kwong, Witold Kycler, Marc Ladanyi, Phillip H. Lai, Peter W. Laird, Eric Lander, Michael S. Lawrence, Alexander J. Lazar, Radoslaw Łaźniak, Darlene Lee, Jeffrey E. Lee, Junehawk Lee, Kenneth Lee, Semin Lee, William Lee, Ewa Leporowska, Kristen M. Leraas, Haiyan I. Li, Tara M. Lichtenberg, Lee Lichtenstein, Pei Lin, Shiyun Ling, Jia Liu, Ouida Liu, Wenbin Liu, Georgina V. Long, Yiling Lu, Singer Ma, Yussanne Ma, Andrzej Mackiewicz, Harshad S. Mahadeshwar, Jared Malke, David Mallery, Georgy M. Manikhas, Graham J. Mann, Marco A. Marra, Brenna Matejka, Michael Mayo, Sousan Mehrabi, Shaowu Meng, Matthew Meyerson, Piotr A. Mieczkowski, John P. Miller, Martin L. Miller, Gordon B. Mills, Fedor Moiseenko, Richard A. Moore, Scott Morris, Carl Morrison, Donald Morton, Stergios Moschos, Lisle E. Mose, Florian L. Muller, Andrew J. Mungall, Dawid Murawa, Pawel Murawa, Bradley A. Murray, Luigi Nezi, Sam Ng, Dana Nicholson, Michael S. Noble, Adeboye Osunkoya, Taofeek K. Owonikoko, Bradley A. Ozenberger, Elena Pagani, Oxana V. Paklina, Angeliki Pantazi, Michael Parfenov, Jeremy Parfitt, Peter J. Park, Woong Yang Park, Joel S. Parker, Francesca Passarelli, Robert Penny, Charles M. Perou, Todd D. Pihl, Olga Potapova, Victor G. Prieto, Alexei Protopopov, Michael J. Quinn, Amie Radenbaugh, Kunal Rai, Suresh S. Ramalingam, Ayush T. Raman, Nilsa C. Ramirez, Ricardo Ramirez, Uma Rao, W. Kimryn Rathmell, Xiaojia Ren, Sheila M. Reynolds, Jeffrey Roach, A. Gordon Robertson, Merrick I. Ross, Jason Roszik, Giandomenico Russo, Gordon Saksena, Charles Saller, Yardena Samuels, Chris Sander, Cindy Sander, George Sandusky, The Cancer Genome Atlas Network

Research output: Contribution to journal › Article › peer-review

2513 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1681-1696
Number of pages	16
Journal	Cell
Volume	161
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2015.05.044
Publication status	Published - 20 Jun 2015
Externally published	Yes

Access to Document

10.1016/j.cell.2015.05.044

Cite this

Akbani, R., Akdemir, K. C., Aksoy, B. A., Albert, M., Ally, A., Amin, S. B., Arachchi, H., Arora, A., Auman, J. T., Ayala, B., Baboud, J., Balasundaram, M., Balu, S., Barnabas, N., Bartlett, J., Bartlett, P., Bastian, B. C., Baylin, S. B., Behera, M., ... The Cancer Genome Atlas Network (2015). Genomic Classification of Cutaneous Melanoma. Cell, 161(7), 1681-1696. https://doi.org/10.1016/j.cell.2015.05.044

@article{c09c78cc75ae4eb99abe07b07de6e0b1,

title = "Genomic Classification of Cutaneous Melanoma",

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.",

author = "Rehan Akbani and Akdemir, {Kadir C.} and Aksoy, {B. Arman} and Monique Albert and Adrian Ally and Amin, {Samirkumar B.} and Harindra Arachchi and Arshi Arora and Auman, {J. Todd} and Brenda Ayala and Julien Baboud and Miruna Balasundaram and Saianand Balu and Nandita Barnabas and John Bartlett and Pam Bartlett and Bastian, {Boris C.} and Baylin, {Stephen B.} and Madhusmita Behera and Dmitry Belyaev and Christopher Benz and Brady Bernard and Rameen Beroukhim and Natalie Bir and Black, {Aaron D.} and Tom Bodenheimer and Lori Boice and Boland, {Genevieve M.} and Riccardo Bono and Bootwalla, {Moiz S.} and Marcus Bosenberg and Jay Bowen and Reanne Bowlby and Bristow, {Christopher A.} and Laura Brockway-Lunardi and Denise Brooks and Jakub Brzezinski and Wiam Bshara and Elizabeth Buda and Burns, {William R.} and Butterfield, {Yaron S.N.} and Michael Button and Tiffany Calderone and Cappellini, {Giancarlo Antonini} and Candace Carter and Carter, {Scott L.} and Lynn Cherney and Cherniack, {Andrew D.} and Aaron Chevalier and Lynda Chin and Juok Cho and Cho, {Raymond J.} and Choi, {Yoon La} and Andy Chu and Sudha Chudamani and Kristian Cibulskis and Giovanni Ciriello and Amanda Clarke and Stephen Coons and Leslie Cope and Daniel Crain and Erin Curley and Ludmila Danilova and Stefania D'Atri and Tanja Davidsen and Davies, {Michael A.} and Delman, {Keith A.} and Demchok, {John A.} and Deng, {Qixia A.} and Deribe, {Yonathan Lissanu} and Noreen Dhalla and Rajiv Dhir and Daniel Dicara and Michael Dinikin and Michael Dubina and Ebrom, {J. Stephen} and Sophie Egea and Greg Eley and Jay Engel and Eschbacher, {Jennifer M.} and Fedosenko, {Konstantin V.} and Ina Felau and Timothy Fennell and Ferguson, {Martin L.} and Sheila Fisher and Flaherty, {Keith T.} and Scott Frazer and Jessica Frick and Victoria Fulidou and Gabriel, {Stacey B.} and Jianjiong Gao and Johanna Gardner and Garraway, {Levi A.} and Gastier-Foster, {Julie M.} and Carmelo Gaudioso and Nils Gehlenborg and Giannicola Genovese and Mark Gerken and Gershenwald, {Jeffrey E.} and Gad Getz and Carmen Gomez-Fernandez and Thomas Gribbin and Jonna Grimsby and Benjamin Gross and Ranabir Guin and Tony Gutschner and Angela Hadjipanayis and Ruth Halaban and Benjamin Hanf and David Haussler and Haydu, {Lauren E.} and Hayes, {D. Neil} and Hayward, {Nicholas K.} and Heiman, {David I.} and Lynn Herbert and Herman, {James G.} and Peter Hersey and Hoadley, {Katherine A.} and Eran Hodis and Holt, {Robert A.} and Hoon, {Dave Sb} and Susan Hoppough and Hoyle, {Alan P.} and Huang, {Franklin W.} and Mei Huang and Sharon Huang and Hutter, {Carolyn M.} and Matthew Ibbs and Lisa Iype and Anders Jacobsen and Valerie Jakrot and Alyssa Janning and Jeck, {William R.} and Jefferys, {Stuart R.} and Jensen, {Mark A.} and Jones, {Corbin D.} and Jones, {Steven J.M.} and Zhenlin Ju and Hojabr Kakavand and Hyojin Kang and Kefford, {Richard F.} and Khuri, {Fadlo R.} and Jaegil Kim and Kirkwood, {John M.} and Joachim Klode and Anil Korkut and Konstanty Korski and Michael Krauthammer and Raju Kucherlapati and Kwong, {Lawrence N.} and Witold Kycler and Marc Ladanyi and Lai, {Phillip H.} and Laird, {Peter W.} and Eric Lander and Lawrence, {Michael S.} and Lazar, {Alexander J.} and Radoslaw {\L}a{\'z}niak and Darlene Lee and Lee, {Jeffrey E.} and Junehawk Lee and Kenneth Lee and Semin Lee and William Lee and Ewa Leporowska and Leraas, {Kristen M.} and Li, {Haiyan I.} and Lichtenberg, {Tara M.} and Lee Lichtenstein and Pei Lin and Shiyun Ling and Jia Liu and Ouida Liu and Wenbin Liu and Long, {Georgina V.} and Yiling Lu and Singer Ma and Yussanne Ma and Andrzej Mackiewicz and Mahadeshwar, {Harshad S.} and Jared Malke and David Mallery and Manikhas, {Georgy M.} and Mann, {Graham J.} and Marra, {Marco A.} and Brenna Matejka and Michael Mayo and Sousan Mehrabi and Shaowu Meng and Matthew Meyerson and Mieczkowski, {Piotr A.} and Miller, {John P.} and Miller, {Martin L.} and Mills, {Gordon B.} and Fedor Moiseenko and Moore, {Richard A.} and Scott Morris and Carl Morrison and Donald Morton and Stergios Moschos and Mose, {Lisle E.} and Muller, {Florian L.} and Mungall, {Andrew J.} and Dawid Murawa and Pawel Murawa and Murray, {Bradley A.} and Luigi Nezi and Sam Ng and Dana Nicholson and Noble, {Michael S.} and Adeboye Osunkoya and Owonikoko, {Taofeek K.} and Ozenberger, {Bradley A.} and Elena Pagani and Paklina, {Oxana V.} and Angeliki Pantazi and Michael Parfenov and Jeremy Parfitt and Park, {Peter J.} and Park, {Woong Yang} and Parker, {Joel S.} and Francesca Passarelli and Robert Penny and Perou, {Charles M.} and Pihl, {Todd D.} and Olga Potapova and Prieto, {Victor G.} and Alexei Protopopov and Quinn, {Michael J.} and Amie Radenbaugh and Kunal Rai and Ramalingam, {Suresh S.} and Raman, {Ayush T.} and Ramirez, {Nilsa C.} and Ricardo Ramirez and Uma Rao and Rathmell, {W. Kimryn} and Xiaojia Ren and Reynolds, {Sheila M.} and Jeffrey Roach and Robertson, {A. Gordon} and Ross, {Merrick I.} and Jason Roszik and Giandomenico Russo and Gordon Saksena and Charles Saller and Yardena Samuels and Chris Sander and Cindy Sander and George Sandusky and {The Cancer Genome Atlas Network}",

year = "2015",

month = jun,

day = "20",

doi = "10.1016/j.cell.2015.05.044",

language = "English",

volume = "161",

pages = "1681--1696",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier",

number = "7",

}

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, YSN, 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, SJM, 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 & The Cancer Genome Atlas Network 2015, 'Genomic Classification of Cutaneous Melanoma', Cell, vol. 161, no. 7, pp. 1681-1696. https://doi.org/10.1016/j.cell.2015.05.044

TY - JOUR

T1 - Genomic Classification of Cutaneous Melanoma

AU - Akbani, Rehan

AU - Akdemir, Kadir C.

AU - Aksoy, B. Arman

AU - Albert, Monique

AU - Ally, Adrian

AU - Amin, Samirkumar B.

AU - Arachchi, Harindra

AU - Arora, Arshi

AU - Auman, J. Todd

AU - Ayala, Brenda

AU - Baboud, Julien

AU - Balasundaram, Miruna

AU - Balu, Saianand

AU - Barnabas, Nandita

AU - Bartlett, John

AU - Bartlett, Pam

AU - Bastian, Boris C.

AU - Baylin, Stephen B.

AU - Behera, Madhusmita

AU - Belyaev, Dmitry

AU - Benz, Christopher

AU - Bernard, Brady

AU - Beroukhim, Rameen

AU - Bir, Natalie

AU - Black, Aaron D.

AU - Bodenheimer, Tom

AU - Boice, Lori

AU - Boland, Genevieve M.

AU - Bono, Riccardo

AU - Bootwalla, Moiz S.

AU - Bosenberg, Marcus

AU - Bowen, Jay

AU - Bowlby, Reanne

AU - Bristow, Christopher A.

AU - Brockway-Lunardi, Laura

AU - Brooks, Denise

AU - Brzezinski, Jakub

AU - Bshara, Wiam

AU - Buda, Elizabeth

AU - Burns, William R.

AU - Butterfield, Yaron S.N.

AU - Button, Michael

AU - Calderone, Tiffany

AU - Cappellini, Giancarlo Antonini

AU - Carter, Candace

AU - Carter, Scott L.

AU - Cherney, Lynn

AU - Cherniack, Andrew D.

AU - Chevalier, Aaron

AU - Chin, Lynda

AU - Cho, Juok

AU - Cho, Raymond J.

AU - Choi, Yoon La

AU - Chu, Andy

AU - Chudamani, Sudha

AU - Cibulskis, Kristian

AU - Ciriello, Giovanni

AU - Clarke, Amanda

AU - Coons, Stephen

AU - Cope, Leslie

AU - Crain, Daniel

AU - Curley, Erin

AU - Danilova, Ludmila

AU - D'Atri, Stefania

AU - Davidsen, Tanja

AU - Davies, Michael A.

AU - Delman, Keith A.

AU - Demchok, John A.

AU - Deng, Qixia A.

AU - Deribe, Yonathan Lissanu

AU - Dhalla, Noreen

AU - Dhir, Rajiv

AU - Dicara, Daniel

AU - Dinikin, Michael

AU - Dubina, Michael

AU - Ebrom, J. Stephen

AU - Egea, Sophie

AU - Eley, Greg

AU - Engel, Jay

AU - Eschbacher, Jennifer M.

AU - Fedosenko, Konstantin V.

AU - Felau, Ina

AU - Fennell, Timothy

AU - Ferguson, Martin L.

AU - Fisher, Sheila

AU - Flaherty, Keith T.

AU - Frazer, Scott

AU - Frick, Jessica

AU - Fulidou, Victoria

AU - Gabriel, Stacey B.

AU - Gao, Jianjiong

AU - Gardner, Johanna

AU - Garraway, Levi A.

AU - Gastier-Foster, Julie M.

AU - Gaudioso, Carmelo

AU - Gehlenborg, Nils

AU - Genovese, Giannicola

AU - Gerken, Mark

AU - Gershenwald, Jeffrey E.

AU - Getz, Gad

AU - Gomez-Fernandez, Carmen

AU - Gribbin, Thomas

AU - Grimsby, Jonna

AU - Gross, Benjamin

AU - Guin, Ranabir

AU - Gutschner, Tony

AU - Hadjipanayis, Angela

AU - Halaban, Ruth

AU - Hanf, Benjamin

AU - Haussler, David

AU - Haydu, Lauren E.

AU - Hayes, D. Neil

AU - Hayward, Nicholas K.

AU - Heiman, David I.

AU - Herbert, Lynn

AU - Herman, James G.

AU - Hersey, Peter

AU - Hoadley, Katherine A.

AU - Hodis, Eran

AU - Holt, Robert A.

AU - Hoon, Dave Sb

AU - Hoppough, Susan

AU - Hoyle, Alan P.

AU - Huang, Franklin W.

AU - Huang, Mei

AU - Huang, Sharon

AU - Hutter, Carolyn M.

AU - Ibbs, Matthew

AU - Iype, Lisa

AU - Jacobsen, Anders

AU - Jakrot, Valerie

AU - Janning, Alyssa

AU - Jeck, William R.

AU - Jefferys, Stuart R.

AU - Jensen, Mark A.

AU - Jones, Corbin D.

AU - Jones, Steven J.M.

AU - Ju, Zhenlin

AU - Kakavand, Hojabr

AU - Kang, Hyojin

AU - Kefford, Richard F.

AU - Khuri, Fadlo R.

AU - Kim, Jaegil

AU - Kirkwood, John M.

AU - Klode, Joachim

AU - Korkut, Anil

AU - Korski, Konstanty

AU - Krauthammer, Michael

AU - Kucherlapati, Raju

AU - Kwong, Lawrence N.

AU - Kycler, Witold

AU - Ladanyi, Marc

AU - Lai, Phillip H.

AU - Laird, Peter W.

AU - Lander, Eric

AU - Lawrence, Michael S.

AU - Lazar, Alexander J.

AU - Łaźniak, Radoslaw

AU - Lee, Darlene

AU - Lee, Jeffrey E.

AU - Lee, Junehawk

AU - Lee, Kenneth

AU - Lee, Semin

AU - Lee, William

AU - Leporowska, Ewa

AU - Leraas, Kristen M.

AU - Li, Haiyan I.

AU - Lichtenberg, Tara M.

AU - Lichtenstein, Lee

AU - Lin, Pei

AU - Ling, Shiyun

AU - Liu, Jia

AU - Liu, Ouida

AU - Liu, Wenbin

AU - Long, Georgina V.

AU - Lu, Yiling

AU - Ma, Singer

AU - Ma, Yussanne

AU - Mackiewicz, Andrzej

AU - Mahadeshwar, Harshad S.

AU - Malke, Jared

AU - Mallery, David

AU - Manikhas, Georgy M.

AU - Mann, Graham J.

AU - Marra, Marco A.

AU - Matejka, Brenna

AU - Mayo, Michael

AU - Mehrabi, Sousan

AU - Meng, Shaowu

AU - Meyerson, Matthew

AU - Mieczkowski, Piotr A.

AU - Miller, John P.

AU - Miller, Martin L.

AU - Mills, Gordon B.

AU - Moiseenko, Fedor

AU - Moore, Richard A.

AU - Morris, Scott

AU - Morrison, Carl

AU - Morton, Donald

AU - Moschos, Stergios

AU - Mose, Lisle E.

AU - Muller, Florian L.

AU - Mungall, Andrew J.

AU - Murawa, Dawid

AU - Murawa, Pawel

AU - Murray, Bradley A.

AU - Nezi, Luigi

AU - Ng, Sam

AU - Nicholson, Dana

AU - Noble, Michael S.

AU - Osunkoya, Adeboye

AU - Owonikoko, Taofeek K.

AU - Ozenberger, Bradley A.

AU - Pagani, Elena

AU - Paklina, Oxana V.

AU - Pantazi, Angeliki

AU - Parfenov, Michael

AU - Parfitt, Jeremy

AU - Park, Peter J.

AU - Park, Woong Yang

AU - Parker, Joel S.

AU - Passarelli, Francesca

AU - Penny, Robert

AU - Perou, Charles M.

AU - Pihl, Todd D.

AU - Potapova, Olga

AU - Prieto, Victor G.

AU - Protopopov, Alexei

AU - Quinn, Michael J.

AU - Radenbaugh, Amie

AU - Rai, Kunal

AU - Ramalingam, Suresh S.

AU - Raman, Ayush T.

AU - Ramirez, Nilsa C.

AU - Ramirez, Ricardo

AU - Rao, Uma

AU - Rathmell, W. Kimryn

AU - Ren, Xiaojia

AU - Reynolds, Sheila M.

AU - Roach, Jeffrey

AU - Robertson, A. Gordon

AU - Ross, Merrick I.

AU - Roszik, Jason

AU - Russo, Giandomenico

AU - Saksena, Gordon

AU - Saller, Charles

AU - Samuels, Yardena

AU - Sander, Chris

AU - Sander, Cindy

AU - Sandusky, George

AU - The Cancer Genome Atlas Network

PY - 2015/6/20

Y1 - 2015/6/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84935009372&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2015.05.044

DO - 10.1016/j.cell.2015.05.044

M3 - Article

C2 - 26091043

AN - SCOPUS:84935009372

SN - 0092-8674

VL - 161

SP - 1681

EP - 1696

JO - Cell

JF - Cell

IS - 7

ER -

Genomic Classification of Cutaneous Melanoma

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