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Nat Genet. 2016 Jun;48(6):607-16. doi: 10.1038/ng.3564. Epub 2016 May 9.

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

Author information

1
Cancer Program, Eli and Edythe L. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
2
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
3
Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA.
4
Computer Technologies Laboratory, ITMO University, St. Petersburg, Russia.
5
Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
6
Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
7
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
8
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
9
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
10
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
11
Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.

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.

Comment in

PMID:
27158780
PMCID:
PMC4884143
DOI:
10.1038/ng.3564
[Indexed for MEDLINE]
Free PMC Article

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