TY - JOUR
T1 - Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas
AU - Campbell, Joshua D.
AU - Alexandrov, Anton
AU - Kim, Jaegil
AU - Wala, Jeremiah
AU - Berger, Alice H.
AU - Pedamallu, Chandra Sekhar
AU - Shukla, Sachet A.
AU - Guo, Guangwu
AU - Brooks, Angela N.
AU - Murray, Bradley A.
AU - Imielinski, Marcin
AU - Hu, Xin
AU - Ling, Shiyun
AU - Akbani, Rehan
AU - Rosenberg, Mara
AU - Cibulskis, Carrie
AU - Ramachandran, Aruna
AU - Collisson, Eric A.
AU - Kwiatkowski, David J.
AU - Lawrence, Michael S.
AU - Weinstein, John N.
AU - Verhaak, Roel G.W.
AU - Wu, Catherine J.
AU - Hammerman, Peter S.
AU - Cherniack, Andrew D.
AU - Getz, Gad
AU - Artyomov, Maxim N.
AU - Schreiber, Robert
AU - Govindan, Ramaswamy
AU - Meyerson, Matthew
N1 - Publisher Copyright:
© 2016 Nature America, Inc.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84966600817&partnerID=8YFLogxK
U2 - 10.1038/ng.3564
DO - 10.1038/ng.3564
M3 - Article
C2 - 27158780
AN - SCOPUS:84966600817
SN - 1061-4036
VL - 48
SP - 607
EP - 616
JO - Nature Genetics
JF - Nature Genetics
IS - 6
ER -