Comprehensive molecular profiling of lung adenocarcinoma: The cancer genome atlas research network
Year: 2020
Type: article
Study design: Observational Study
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.
DOI: 10.17615/s7re-zq82
Authors: Travis, William D., Ladanyi, Marc, Lee, William, Beer, David G., Hernandez, Bryan, Kwiatkowski, David, Tsao, Ming-Sound, Campbell, Joshua D., Jurisica, Igor, Chu, Andy, Berger, Alice H., Hammerman, Peter S., Robertson, Gordon, Kucherlapati, Raju, Collisson, Eric A., Schultz, Nikolaus, Danilova, Ludmila, Sougnez, Carrie, Getz, Gad, Shen, Ronglai, Creighton, Chad J., Weinstein, John N., Heymach, John V., Cope, Leslie, Wigle, Dennis A., Wilkerson, Matthew D., Brooks, Angela N., Neil Hayes, D., Ding, Li, Sinha, Rileen, Chmielecki, Juliann, Herman, James G.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1083213090, G139585312, G2049268772, G2659503640, G2664783788, G2851467072, G2857508635, G2894286751, G3331582980, G3746653997, The Human Genome Sequencing Center, Harvard Genome Characterization Center, G5005221876, Cancer transcriptome characterization using massively parallel DNA sequencing, G5181012032, G5711250986, G7097003521, G9000018409, G9000019010, G9000022338, G9000022781, G9000033506, G9000048103, G9000052705, G9000062434, G9000079746, G9000086836, G9000176922, G9000179146, G9000186802, G9000193931, G9000244592, G9000305565
OpenAlex ID: W4298328151