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

Nat Genet
Authors
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.

Year of Publication
2016
Journal
Nat Genet
Volume
48
Issue
6
Pages
607-16
Date Published
2016 Jun
ISSN
1546-1718
URL
DOI
10.1038/ng.3564
PubMed ID
27158780
PubMed Central ID
PMC4884143
Links
Grant list
K99 CA197762 / CA / NCI NIH HHS / United States
K08 CA163677 / CA / NCI NIH HHS / United States
P01 CA120964 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
T32 HG002295 / HG / NHGRI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
R01 CA155010 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
R35 CA197568 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA199461 / CA / NCI NIH HHS / United States
U24 CA126546 / CA / NCI NIH HHS / United States
U24 CA126544 / CA / NCI NIH HHS / United States