Comprehensive molecular profiling of lung adenocarcinoma.
Details
State: Public
Version: Author's accepted manuscript
License: CC BY-NC-SA 4.0
Serval ID
serval:BIB_AD462EA7A7F2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Comprehensive molecular profiling of lung adenocarcinoma.
Journal
Nature
Working group(s)
Cancer Genome Atlas Research Network
Contributor(s)
Collisson E. A., Campbell J.D., Brooks A.N., Berger A.H., Lee W., Chmielecki J., Beer D.G., Cope L., Creighton C.J., Danilova L., Ding L., Getz G., Hammerman P.S., Hayes D.N., Hernandez B., Herman J.G., Heymach J.V., Jurisica I., Kucherlapati R., Kwiatkowski D., Ladanyi M., Robertson G., Schultz N., Shen R., Sinha R., Sougnez C., Tsao M.S., Travis W.D., Weinstein J.N., Wigle D.A., Wilkerson M.D., Chu A., Cherniack A.D., Hadjipanayis A., Rosenberg M., Weisenberger D.J., Laird P.W., Radenbaugh A., Ma S., Stuart J.M., Averett Byers L., Baylin S.B., Govindan R., Meyerson M., Rosenberg M., Gabriel S.B., Cibulskis K., Sougnez C., Kim J., Stewart C., Lichtenstein L., Lander E.S., Lawrence M.S., Getz G., Kandoth C., Fulton R., Fulton L.L., McLellan M.D., Wilson R.K., Ye K., Fronick C.C., Maher C.A., Miller C.A., Wendl M.C., Cabanski C., Ding L., Mardis E., Govindan R., Creighton C.J., Wheeler D., Balasundaram M., Butterfield Y.S., Carlsen R., Chu A., Chuah E., Dhalla N., Guin R., Hirst C., Lee D., Li H.I., Mayo M., Moore R.A., Mungall A.J., Schein J.E., Sipahimalani P., Tam A., Varhol R., Robertson A., Wye N., Thiessen N., Holt R.A., Jones S.J., Marra M.A., Campbell J.D., Brooks A.N., Chmielecki J., Imielinski M., Onofrio R.C., Hodis E., Zack T., Sougnez C., Helman E., Sekhar Pedamallu C., Mesirov J., Cherniack A.D., Saksena G., Schumacher S.E., Carter S.L., Hernandez B., Garraway L., Beroukhim R., Gabriel S.B., Getz G., Meyerson M., Hadjipanayis A., Lee S., Mahadeshwar H.S., Pantazi A., Protopopov A., Ren X., Seth S., Song X., Tang J., Yang L., Zhang J., Chen P.C., Parfenov M., Wei Xu A., Santoso N., Chin L., Park P.J., Kucherlapati R., Hoadley K.A., Auman J.T., Meng S., Shi Y., Buda E., Waring S., Veluvolu U., Tan D., Mieczkowski P.A., Jones C.D., Simons J.V., Soloway M.G., Bodenheimer T., Jefferys S.R., Roach J., Hoyle A.P., Wu J., Balu S., Singh D., Prins J.F., Marron J.S., Parker J.S., Hayes D.N., Perou C.M., Liu J., Cope L., Danilova L., Weisenberger D.J., Maglinte D.T., Lai P.H., Bootwalla M.S., Van Den Berg D.J., Triche T., Baylin S.B., Laird P.W., Rosenberg M., Chin L., Zhang J., Cho J., DiCara D., Heiman D., Lin P., Mallard W., Voet D., Zhang H., Zou L., Noble M.S., Lawrence M.S., Saksena G., Gehlenborg N., Thorvaldsdottir H., Mesirov J., Nazaire M.D., Robinson J., Getz G., Lee W., Aksoy B.A., Ciriello G., Taylor B.S., Dresdner G., Gao J., Gross B., Seshan V.E., Ladanyi M., Reva B., Sinha R., Sumer S.O., Weinhold N., Schultz N., Shen R., Sander C., Ng S., Ma S., Zhu J., Radenbaugh A., Stuart J.M., Benz C.C., Yau C., Haussler D., Spellman P.T., Wilkerson M.D., Parker J.S., Hoadley K.A., Kimes P.K., Hayes D.N., Perou C.M., Broom B.M., Wang J., Lu Y., Kwok Shing Ng P., Diao L., Averett Byers L., Liu W., Heymach J.V., Amos C.I., Weinstein J.N., Akbani R., Mills G.B., Curley E., Paulauskis J., Lau K., Morris S., Shelton T., Mallery D., Gardner J., Penny R., Saller C., Tarvin K., Richards W.G., Cerfolio R., Bryant A., Raymond D.P., Pennell N.A., 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 K.V., Gal A., Behera M., Ramalingam S.S., 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 M.V., Williamson C., Burks E., Rieger-Christ K., Holway A., Sullivan T., Wigle D.A., Asiedu M.K., Kosari F., Travis W.D., Rekhtman N., Zakowski M., Rusch V.W., Zippile P., Suh J., Pass H., Goparaju C., Owusu-Sarpong Y., Bartlett J.M., Kodeeswaran S., Parfitt J., Sekhon H., Albert M., Eckman J., Myers J.B., Cheney R., Morrison C., Gaudioso C., Borgia J.A., Bonomi P., Pool M., Liptay M.J., Moiseenko F., Zaytseva I., Dienemann H., Meister M., Schnabel P.A., Muley T.R., Peifer M., Gomez-Fernandez C., Herbert L., Egea S., Huang M., Thorne L.B., Boice L., Hill Salazar A., Funkhouser W.K., Rathmell W.K., Dhir R., Yousem S.A., Dacic S., Schneider F., Siegfried J.M., Hajek R., Watson M.A., McDonald S., Meyers B., Clarke B., Yang I.A., Fong K.M., Hunter L., Windsor M., Bowman R.V., Peters S., Letovanec I., Khan K.Z., Jensen M.A., Snyder E.E., Srinivasan D., Kahn A.B., Baboud J., Pot D.A., Mills Shaw K.R., Sheth M., Davidsen T., Demchok J.A., Yang L., Wang Z., Tarnuzzer R., Zenklusen J.C., Ozenberger B.A., Sofia H.J., Travis W.D., Cheney R., Clarke B., Dacic S., Duhig E., Funkhouser W.K., Illei P., Farver C., Rekhtman N., Sica G., Suh J., Tsao M.S., Travis W.D., Cheney R., Clarke B., Dacic S., Duhig E., Funkhouser W.K., Illei P., Farver C., Rekhtman N., Sica G., Suh J., Tsao M.S.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
31/07/2014
Peer-reviewed
Oui
Volume
511
Number
7511
Pages
543-550
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
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.
Keywords
Adenocarcinoma/genetics, Adenocarcinoma/pathology, Cell Cycle Proteins/genetics, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genomics, Humans, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Male, Molecular Typing, Mutation/genetics, Oncogenes/genetics, Sex Factors, Transcriptome/genetics
Pubmed
Web of science
Open Access
Yes
Create date
20/10/2014 9:22
Last modification date
20/08/2019 16:17
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