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 | |
| Publication status | Published - 20 Jun 2015 |
| Externally published | Yes |
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Genomic Classification of Cutaneous Melanoma. / Akbani, Rehan; Akdemir, Kadir C.; Aksoy, B. Arman; Albert, Monique; Ally, Adrian; Amin, Samirkumar B.; Arachchi, Harindra; Arora, Arshi; Auman, J. Todd; Ayala, Brenda; Baboud, Julien; Balasundaram, Miruna; Balu, Saianand; Barnabas, Nandita; Bartlett, John; Bartlett, Pam; Bastian, Boris C.; Baylin, Stephen B.; Behera, Madhusmita; Belyaev, Dmitry; Benz, Christopher; Bernard, Brady; Beroukhim, Rameen; Bir, Natalie; Black, Aaron D.; Bodenheimer, Tom; Boice, Lori; Boland, Genevieve M.; Bono, Riccardo; Bootwalla, Moiz S.; Bosenberg, Marcus; Bowen, Jay; Bowlby, Reanne; Bristow, Christopher A.; Brockway-Lunardi, Laura; Brooks, Denise; Brzezinski, Jakub; Bshara, Wiam; Buda, Elizabeth; Burns, William R.; Butterfield, Yaron S.N.; Button, Michael; Calderone, Tiffany; Cappellini, Giancarlo Antonini; Carter, Candace; Carter, Scott L.; Cherney, Lynn; Cherniack, Andrew D.; Chevalier, Aaron; Chin, Lynda; Cho, Juok; Cho, Raymond J.; Choi, Yoon La; Chu, Andy; Chudamani, Sudha; Cibulskis, Kristian; Ciriello, Giovanni; Clarke, Amanda; Coons, Stephen; Cope, Leslie; Crain, Daniel; Curley, Erin; Danilova, Ludmila; D'Atri, Stefania; Davidsen, Tanja; Davies, Michael A.; Delman, Keith A.; Demchok, John A.; Deng, Qixia A.; Deribe, Yonathan Lissanu; Dhalla, Noreen; Dhir, Rajiv; Dicara, Daniel; Dinikin, Michael; Dubina, Michael; Ebrom, J. Stephen; Egea, Sophie; Eley, Greg; Engel, Jay; Eschbacher, Jennifer M.; Fedosenko, Konstantin V.; Felau, Ina; Fennell, Timothy; Ferguson, Martin L.; Fisher, Sheila; Flaherty, Keith T.; Frazer, Scott; Frick, Jessica; Fulidou, Victoria; Gabriel, Stacey B.; Gao, Jianjiong; Gardner, Johanna; Garraway, Levi A.; Gastier-Foster, Julie M.; Gaudioso, Carmelo; Gehlenborg, Nils; Genovese, Giannicola; Gerken, Mark; Gershenwald, Jeffrey E.; Getz, Gad; Gomez-Fernandez, Carmen; Gribbin, Thomas; Grimsby, Jonna; Gross, Benjamin; Guin, Ranabir; Gutschner, Tony; Hadjipanayis, Angela; Halaban, Ruth; Hanf, Benjamin; Haussler, David; Haydu, Lauren E.; Hayes, D. Neil; Hayward, Nicholas K.; Heiman, David I.; Herbert, Lynn; Herman, James G.; Hersey, Peter; Hoadley, Katherine A.; Hodis, Eran; Holt, Robert A.; Hoon, Dave Sb; Hoppough, Susan; Hoyle, Alan P.; Huang, Franklin W.; Huang, Mei; Huang, Sharon; Hutter, Carolyn M.; Ibbs, Matthew; Iype, Lisa; Jacobsen, Anders; Jakrot, Valerie; Janning, Alyssa; Jeck, William R.; Jefferys, Stuart R.; Jensen, Mark A.; Jones, Corbin D.; Jones, Steven J.M.; Ju, Zhenlin; Kakavand, Hojabr; Kang, Hyojin; Kefford, Richard F.; Khuri, Fadlo R.; Kim, Jaegil; Kirkwood, John M.; Klode, Joachim; Korkut, Anil; Korski, Konstanty; Krauthammer, Michael; Kucherlapati, Raju; Kwong, Lawrence N.; Kycler, Witold; Ladanyi, Marc; Lai, Phillip H.; Laird, Peter W.; Lander, Eric; Lawrence, Michael S.; Lazar, Alexander J.; Łaźniak, Radoslaw; Lee, Darlene; Lee, Jeffrey E.; Lee, Junehawk; Lee, Kenneth; Lee, Semin; Lee, William; Leporowska, Ewa; Leraas, Kristen M.; Li, Haiyan I.; Lichtenberg, Tara M.; Lichtenstein, Lee; Lin, Pei; Ling, Shiyun; Liu, Jia; Liu, Ouida; Liu, Wenbin; Long, Georgina V.; Lu, Yiling; Ma, Singer; Ma, Yussanne; Mackiewicz, Andrzej; Mahadeshwar, Harshad S.; Malke, Jared; Mallery, David; Manikhas, Georgy M.; Mann, Graham J.; Marra, Marco A.; Matejka, Brenna; Mayo, Michael; Mehrabi, Sousan; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Miller, John P.; Miller, Martin L.; Mills, Gordon B.; Moiseenko, Fedor; Moore, Richard A.; Morris, Scott; Morrison, Carl; Morton, Donald; Moschos, Stergios; Mose, Lisle E.; Muller, Florian L.; Mungall, Andrew J.; Murawa, Dawid; Murawa, Pawel; Murray, Bradley A.; Nezi, Luigi; Ng, Sam; Nicholson, Dana; Noble, Michael S.; Osunkoya, Adeboye; Owonikoko, Taofeek K.; Ozenberger, Bradley A.; Pagani, Elena; Paklina, Oxana V.; Pantazi, Angeliki; Parfenov, Michael; Parfitt, Jeremy; Park, Peter J.; Park, Woong Yang; Parker, Joel S.; Passarelli, Francesca; Penny, Robert; Perou, Charles M.; Pihl, Todd D.; Potapova, Olga; Prieto, Victor G.; Protopopov, Alexei; Quinn, Michael J.; Radenbaugh, Amie; Rai, Kunal; Ramalingam, Suresh S.; Raman, Ayush T.; Ramirez, Nilsa C.; Ramirez, Ricardo; Rao, Uma; Rathmell, W. Kimryn; Ren, Xiaojia; Reynolds, Sheila M.; Roach, Jeffrey; Robertson, A. Gordon; Ross, Merrick I.; Roszik, Jason; Russo, Giandomenico; Saksena, Gordon; Saller, Charles; Samuels, Yardena; Sander, Chris; Sander, Cindy; Sandusky, George; The Cancer Genome Atlas Network.
In: Cell, Vol. 161, No. 7, 20.06.2015, p. 1681-1696.Research output: Contribution to journal › Article › peer-review
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
VL - 161
SP - 1681
EP - 1696
JO - Cell
JF - Cell
SN - 0092-8674
IS - 7
ER -