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Nature. 2014 Jul 31;511(7511):543-50. doi: 10.1038/nature13385. Epub 2014 Jul 9.

Comprehensive molecular profiling of lung adenocarcinoma.

Collaborators (383)

Collisson EA, Campbell JD, Brooks AN, Berger AH, Lee W, Chmielecki J, Beer DG, Cope L, Creighton CJ, Danilova L, Ding L, Getz G, Hammerman PS, Hayes DN, Hernandez B, Herman JG, Heymach JV, Jurisica I, Kucherlapati R, Kwiatkowski D, Ladanyi M, Robertson G, Schultz N, Shen R, Sinha R, Sougnez C, Tsao MS, Travis WD, Weinstein JN, Wigle DA, Wilkerson MD, Chu A, Cherniack AD, Hadjipanayis A, Rosenberg M, Weisenberger DJ, Laird PW, Radenbaugh A, Ma S, Stuart JM, Averett Byers L, Baylin SB, Govindan R, Meyerson M, Rosenberg M, Gabriel SB, Cibulskis K, Sougnez C, Kim J, Stewart C, Lichtenstein L, Lander ES, Lawrence MS, Getz, Kandoth C, Fulton R, Fulton LL, McLellan MD, Wilson RK, Ye K, Fronick CC, Maher CA, Miller CA, Wendl MC, Cabanski C, Ding L, Mardis E, Govindan R, Creighton CJ, Wheeler D, Balasundaram M, Butterfield YS, Carlsen R, Chu A, Chuah E, Dhalla N, Guin R, Hirst C, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ, Schein JE, Sipahimalani P, Tam A, Varhol R, Robertson A, Wye N, Thiessen N, Holt RA, Jones SJ, Marra MA, Campbell JD, Brooks AN, Chmielecki J, Imielinski M, Onofrio RC, Hodis E, Zack T, Sougnez C, Helman E, Sekhar Pedamallu C, Mesirov J, Cherniack AD, Saksena G, Schumacher SE, Carter SL, Hernandez B, Garraway L, Beroukhim R, Gabriel SB, Getz G, Meyerson M, Hadjipanayis A, Lee S, Mahadeshwar HS, Pantazi A, Protopopov A, Ren X, Seth S, Song X, Tang J, Yang L, Zhang J, Chen PC, Parfenov M, Wei Xu A, Santoso N, Chin L, Park PJ, Kucherlapati R, Hoadley KA, Auman JT, Meng S, Shi Y, Buda E, Waring S, Veluvolu U, Tan D, Mieczkowski PA, Jones CD, Simons JV, Soloway MG, Bodenheimer T, Jefferys SR, Roach J, Hoyle AP, Wu J, Balu S, Singh D, Prins JF, Marron JS, Parker JS, Hayes DN, Perou CM, Liu J, Cope L, Danilova L, Weisenberger DJ, Maglinte DT, Lai PH, Bootwalla MS, Van Den Berg DJ, Triche T Jr, Baylin SB, Laird PW, Rosenberg M, Chin L, Zhang J, Cho J, DiCara D, Heiman D, Lin P, Mallard W, Voet D, Zhang H, Zou L, Noble MS, Lawrence MS, Saksena G, Gehlenborg N, Thorvaldsdottir H, Mesirov J, Nazaire MD, Robinson J, Getz G, Lee W, Aksoy BA, Ciriello G, Taylor BS, Dresdner G, Gao J, Gross B, Seshan VE, Ladanyi M, Reva B, Sinha R, Sumer SO, Weinhold N, Schultz N, Shen R, Sander C, Ng S, Ma S, Zhu J, Radenbaugh A, Stuart JM, Benz CC, Yau C, Haussler D, Spellman PT, Wilkerson MD, Parker JS, Hoadley KA, Kimes PK, Hayes DN, Perou CM, Broom BM, Wang J, Lu Y, Kwok Shing Ng P, Diao L, Averett Byers L, Liu W, Heymach JV, Amos CI, Weinstein JN, Akbani R, Mills GB, Curley E, Paulauskis J, Lau K, Morris S, Shelton T, Mallery D, Gardner J, Penny R, Saller C, Tarvin K, Richards WG, Cerfolio R, Bryant A, Raymond DP, Pennell NA, Farver C, Czerwinski C, Huelsenbeck-Dill L, Iacocca M, Petrelli N, Rabeno B, Brown J, Bauer T, Dolzhanskiy O, Potapova O, Rotin D, Voronina O, Nemirovich-Danchenko E, Fedosenko KV, Gal A, Behera M, Ramalingam SS, Sica G, Flieder D, Boyd J, Weaver J, Kohl B, Huy Quoc Thinh D, Sandusky G, Juhl H, Duhig E, Illei P, Gabrielson E, Shin J, Lee B, Rodgers K, Trusty D, Brock MV, Williamson C, Burks E, Rieger-Christ K, Holway A, Sullivan T, Wigle DA, Asiedu MK, Kosari F, Travis WD, Rekhtman N, Zakowski M, Rusch VW, Zippile P, Suh J, Pass H, Goparaju C, Owusu-Sarpong Y, Bartlett JM, Kodeeswaran S, Parfitt J, Sekhon H, Albert M, Eckman J, Myers JB, Cheney R, Morrison C, Gaudioso C, Borgia JA, Bonomi P, Pool M, Liptay MJ, Moiseenko F, Zaytseva I, Dienemann H, Meister M, Schnabel PA, Muley TR, Peifer M, Gomez-Fernandez C, Herbert L, Egea S, Huang M, Thorne LB, Boice L, Hill Salazar A, Funkhouser WK, Rathmell WK, Dhir R, Yousem SA, Dacic S, Schneider F, Siegfried JM, Hajek R, Watson MA, McDonald S, Meyers B, Clarke B, Yang IA, Fong KM, Hunter L, Windsor M, Bowman RV, Peters S, Letovanec I, Khan KZ, Jensen MA, Snyder EE, Srinivasan D, Kahn AB, Baboud J, Pot DA, Mills Shaw KR, Sheth M, Davidsen T, Demchok JA, Yang L, Wang Z, Tarnuzzer R, Zenklusen JC, Ozenberger BA, Sofia HJ, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS, Travis WD, Cheney R, Clarke B, Dacic S, Duhig E, Funkhouser WK, Illei P, Farver C, Rekhtman N, Sica G, Suh J, Tsao MS.

Erratum in

  • Nature. 2014 Oct 9;514(7521):262. Rogers, K [corrected to Rodgers, K].

Abstract

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

PMID:
25079552
PMCID:
PMC4231481
DOI:
10.1038/nature13385
[Indexed for MEDLINE]
Free PMC Article

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