Lung squamous cell carcinoma is a common type
of lung cancer, causing approximately 400,000 deaths per year worldwide.
Genomic alterations in squamous cell lung cancers have not been comprehensively
characterized, and no molecularly targeted agents have been specifically
developed for its treatment. As part of The Cancer Genome Atlas, here we
profile 178 lung squamous cell carcinomas to provide a comprehensive landscape
of genomic and epigenomic alterations. We show that the tumour type is
characterized by complex genomic alterations, with a mean of 360 exonic
mutations, 165 genomic rearrangements, and 323 segments of copy number
alteration per tumour. We find statistically recurrent mutations in 11 genes,
including mutation of TP53 in nearly all specimens. Previously unreported
loss-of-function mutations are seen in the HLA-A class I major
histocompatibility gene. Significantly altered pathways included NFE2L2 and
KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH
kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We
identified a potential therapeutic target in most tumours, offering new avenues
of investigation for the treatment of squamous cell lung cancers.
Source : Comprehensive genomic
characterization of squamous cell lung cancers. The Cancer Genome Atlas
Research Network; (Participants are arranged by area of contribution and then
by institution.); Genome sequencing centres: Broad Institute, Hammerman PS,
Lawrence MS, Voet D, Jing R, Cibulskis K, Sivachenko A, Stojanov P, McKenna A,
Lander ES, Gabriel S, Getz G, Sougnez C, Imielinski M, Helman E, Hernandez B,
Pho NH, Meyerson M; Genome characterization centres: BC Cancer Agency, Chu A , Chun HJ, Mungall AJ,
Pleasance E, Gordon Robertson A, Sipahimalani P, Stoll D, Balasundaram M, Birol
I, Butterfield YS, Chuah E, Coope RJ, Corbett R, Dhalla N, Guin R, He A, Hirst
C, Hirst M, Holt RA, Lee D, Li HI, Mayo M, Moore RA, Mungall K, Ming Nip K,
Olshen A, Schein JE, Slobodan JR, Tam A, Thiessen N, Varhol R, Zeng T, Zhao Y,
Jones SJ, Marra MA; Broad Institute, Saksena G, Cherniack AD, Schumacher SE,
Tabak B, Carter SL, Pho NH, Nguyen H, Onofrio RC, Crenshaw A, Ardlie K,
Beroukhim R, Winckler W, Hammerman PS, Getz G, Meyerson M; Brigham &
Women’s Hospital/Harvard Medical School, Protopopov A, Zhang J, Hadjipanayis A,
Lee S, Xi R, Yang L, Ren X, Zhang H, Shukla S, Chen PC, Haseley P, Lee E, Chin
L, Park PJ, Kucherlapati R; Memorial Sloan-Kettering Cancer Center (TCGA pilot
phase only), Socci ND, Liang Y, Schultz N, Borsu L, Lash AE, Viale A, Sander C,
Ladanyi M; University of North Carolina at Chapel Hill, Todd Auman J, Hoadley
KA, Wilkerson MD, Shi Y, Liquori C, Meng S, Li L, Turman YJ, Topal MD, Tan D,
Waring S, Buda E, Walsh J, Jones CD, Mieczkowski PA, Singh D, Wu J, Gulabani A,
Dolina P, Bodenheimer T, Hoyle AP, Simons JV, Soloway MG, Mose LE, Jefferys SR,
Balu S, O'Connor BD, Prins JF, Liu J, Chiang DY, Neil Hayes D, Perou CM;
University of Southern California/Johns Hopkins, Cope L, Danilova L,
Weisenberger DJ, Maglinte DT, Pan F, Van Den Berg DJ, Triche Jr T, Herman JG,
Baylin SB, Laird PW; Genome data analysis centres: Broad Institute, Getz G,
Noble M, Voet D, Saksena G, Gehlenborg N, Dicara D, Zhang J, Zhang H, Wu CJ,
Yingchun Liu S, Lawrence MS, Zou L, Sivachenko A, Lin P, Stojanov P, Jing R,
Cho J, Nazaire MD, Robinson J, Thorvaldsdottir H, Mesirov J, Park PJ, Chin L;
Memorial Sloan-Kettering Cancer Center, Schultz N, Sinha R, Ciriello G, Cerami
E, Gross B, Jacobsen A, Gao J, Arman Aksoy B, Weinhold N, Ramirez R, Taylor BS,
Antipin Y, Reva B, Shen R, Mo Q, Seshan V, Paik PK, Ladanyi M, Sander C; The
University of Texas MD Anderson Cancer Center, Akbani R, Zhang N, Broom BM,
Casasent T, Unruh A, Wakefield C, Craig Cason R, Baggerly KA, Weinstein JN;
University of California Santa Cruz/Buck Institute, Haussler D, Benz CC, Stuart
JM, Zhu J, Szeto C, Scott GK, Yau C, Ng S, Goldstein T, Waltman P, Sokolov A,
Ellrott K, Collisson EA, Zerbino D, Wilks C, Ma S, Craft B; University of North
Carolina at Chapel Hill, Wilkerson MD, Todd Auman J, Hoadley KA, Du Y, Cabanski
C, Walter V, Singh D, Wu J, Gulabani A, Bodenheimer T, Hoyle AP, Simons JV,
Soloway MG, Mose LE, Jefferys SR,
Balu S, Marron JS, Liu Y, Wang K, Liu J, Prins JF, Neil Hayes D, Perou CM;
Baylor College of Medicine, Creighton CJ, Zhang Y; Pathology committee, Travis
WD, Rekhtman N, Yi J, Aubry MC, Cheney R, Dacic S, Flieder D, Funkhouser W,
Illei P, Myers J, Tsao MS; Biospecimen core resources: International Genomics
Consortium, Penny R, Mallery D, Shelton T, Hatfield M, Morris S, Yena P,
Shelton C, Sherman M, Paulauskis J; Disease working group, Meyerson M, Baylin
SB, Govindan R, Akbani R, Azodo I, Beer D, Bose R, Byers LA, Carbone D, Chang
LW, Chiang D, Chu A ,
Chun E, Collisson E, Cope L, Creighton CJ, Danilova L, Ding L, Getz G,
Hammerman PS, Neil Hayes D, Hernandez B, Herman JG, Heymach J, Ida C,
Imielinski M, Johnson B, Jurisica I, Kaufman J, Kosari F, Kucherlapati R,
Kwiatkowski D, Ladanyi M, Lawrence MS, Maher CA, Mungall A, Ng S, Pao W, Peifer
M, Penny R, Robertson G, Rusch V, Sander C, Schultz N, Shen R, Siegfried J,
Sinha R, Sivachenko A, Sougnez C, Stoll D, Stuart J, Thomas RK, Tomaszek S,
Tsao MS, Travis WD, Vaske C, Weinstein JN, Weisenberger D, Wigle DA, Wilkerson
MD, Wilks C, Yang P, John Zhang J; Data coordination centre, Jensen MA, Sfeir
R, Kahn AB, Chu AL ,
Kothiyal P, Wang Z, Snyder EE, Pontius J, Pihl TD, Ayala B, Backus M, Walton J,
Baboud J, Berton DL, Nicholls MC, Srinivasan D, Raman R, Girshik S, Kigonya PA,
Alonso S, Sanbhadti RN, Barletta SP, Greene JM, Pot DA; Tissue source sites,
Tsao MS, Bandarchi-Chamkhaleh B, Boyd J, Weaver J, Wigle DA, Azodo IA, Tomaszek
SC, Christine Aubry M, Ida CM, Yang P, Kosari F, Brock MV, Rogers K, Rutledge
M, Brown T, Lee B, Shin J, Trusty D, Dhir R, Siegfried JM, Potapova O,
Fedosenko KV, Nemirovich-Danchenko E, Rusch V, Zakowski M, Iacocca MV, Brown J,
Rabeno B, Czerwinski C, Petrelli N, Fan Z, Todaro N, Eckman J, Myers J, Kimryn
Rathmell W, Thorne LB, Huang M, Boice L, Hill A, Penny R, Mallery D, Curley E,
Shelton C, Yena P, Morrison C, Gaudioso C, Bartlett JM, Kodeeswaran S, Zanke B,
Sekhon H, David K, Juhl H, Van Le X, Kohl B, Thorp R, Viet Tien N, Van Bang N,
Sussman H, Duc Phu B, Hajek R, Phi Hung N, Khan KZ, Muley T; Project team:
National Cancer Institute, Mills Shaw KR, Sheth M, Yang L, Buetow K, Davidsen
T, Demchok JA, Eley G, Ferguson M, Dillon LA, Schaefer C; National Human Genome
Research Institute, Guyer MS, Ozenberger BA, Palchik JD, Peterson J, Sofia HJ,
Thomson E; Writing committee, Hammerman PS, Neil Hayes D, Wilkerson MD, Schultz
N, Bose R, Chu A ,
Collisson EA, Cope L, Creighton CJ, Getz G, Herman JG, Johnson BE, Kucherlapati
R, Ladanyi M, Maher CA, Robertson G, Sander C, Shen R, Sinha R, Sivachenko A,
Thomas RK, Travis WD, Tsao MS, Weinstein JN, Wigle DA, Baylin SB, Govindan R,
Meyerson M. Nature. 2012 Sep 9.
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