Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas

Joshua D. Campbell, Anton Alexandrov, Jaegil Kim, Jeremiah Wala, Alice H. Berger, Chandra Sekhar Pedamallu, Sachet A. Shukla, Guangwu Guo, Angela N. Brooks, Bradley A. Murray, Marcin Imielinski, Xin Hu, Shiyun Ling, Rehan Akbani, Mara Rosenberg, Carrie Cibulskis, Aruna Ramachandran, Eric A. Collisson, David J. Kwiatkowski, Michael S. LawrenceJohn N. Weinstein, Roel G.W. Verhaak, Catherine J. Wu, Peter S. Hammerman, Andrew D. Cherniack, Gad Getz, Maxim N. Artyomov, Robert Schreiber, Ramaswamy Govindan, Matthew Meyerson

Research output: Contribution to journalArticlepeer-review

397 Scopus citations

Abstract

To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. New amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase-Ras-Raf pathway alterations had mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least five predicted neoepitopes. Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes.

Original languageEnglish
Pages (from-to)607-616
Number of pages10
JournalNature Genetics
Volume48
Issue number6
DOIs
StatePublished - Jun 1 2016

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