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.
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This work was supported by grants from the National Cancer Institute as part of The Cancer Genome Atlas project: U24CA126546, U24CA143867, U24CA143845, U24CA126544, and U24CA143883. Additionally, this work was funded by National Cancer Institute grant K08CA163677 (P.S.H.), grant 074-U01 from the government of the Russian Federation (A.A.), US Department of Defense contract W81XWH-12-1-0269 (M.M.), the American Cancer Society Research Professor Award (M.M.), and National Cancer Institute grant R35CA197568 (M.M.).
Some authors received research support from Bayer Pharmaceuticals (C.S.P., B.A.M., A.D.C., and M.M.).
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Campbell, J., Alexandrov, A., Kim, J. et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet 48, 607–616 (2016). https://doi.org/10.1038/ng.3564
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