Nature. 2012 Sep 27;489(7417):519-25. doi: 10.1038/nature11404. Epub 2012 Sep 9.

Comprehensive genomic characterization of squamous cell lung cancers.

Collaborators (412)

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, Chu A, Chun HJ, Mungall AJ, Pleasance E, 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, Nip KM, Olshen A, Schein JE, Slobodan JR, Tam A, Thiessen N, Varhol R, Zeng T, Zhao Y, Jones SJ, Marra MA, 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, 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, Socci ND, Liang Y, Schultz N, Borsu L, Lash AE, Viale A, Sander C, Ladanyi M, Auman T, 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, Hayes D, Perou CM, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Pan F, Van Den Berg DJ, Triche T Jr, Herman JG, Baylin SB, Laird PW, Getz G, Noble M, Voet D, Saksena G, Gehlenborg N, DiCara D, Zhang J, Zhang H, Wu CJ, Liu SY, 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, Schultz N, Sinha R, Ciriello G, Cerami E, Gross B, Jacobsen A, Gao J, Aksoy B, Weinhold N, Ramirez R, Taylor BS, Antipin Y, Reva B, Shen R, Mo Q, Seshan V, Paik PK, Ladanyi M, Sander C, Akbani R, Zhang N, Broom BM, Casasent T, Unruh A, Wakefield C, Cason R, Baggerly KA, Weinstein JN, 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, Wilkerson MD, 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 J, Liu Y, Wang K, Liu J, Prins JF, Hayes D, Perou CM, Creighton CJ, Zhang Y, Travis WD, Rekhtman N, Yi J, Aubry MC, Cheney R, Dacic S, Flieder D, Funkhouser W, Illei P, Myers J, Tsao MS, Penny R, Mallery D, Shelton T, Hatfield M, Morris S, Yena P, Shelton C, Sherman M, Paulauskis J, 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, 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, Wheeler D, Wigle DA, Wilkerson MD, Wilks C, Yang P, Zhang JJ, 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, Tsao MS, Bandarchi-Chamkhaleh B, Boyd J, Weaver J, Wigle DA, Azodo IA, Tomaszek SC, Aubry MC, Ida CM, Yang P, Kosari F, Brock MV, Rodgers 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, 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, Nguyen VT, Nguyen VB, Sussman H, Phu BD, Hajek R, Nguyen PH, Khan KZ, Muley T, Shaw KR, Sheth M, Yang L, Buetow K, Davidsen T, Demchok JA, Eley G, Ferguson M, Dillon LA, Schaefer C, Guyer MS, Ozenberger BA, Palchik JD, Peterson J, Sofia HJ, Thomson E.

Source

Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA.

Erratum in

Nature. 2012 Nov 8;491(7423):288. Rogers, Kristen [corrected to Rodgers, Kristen].

Abstract

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.