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. Lawrence; John 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

doi:10.1038/ng.3564

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

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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 language	English (US)
Pages (from-to)	607-616
Number of pages	10
Journal	Nature Genetics
Volume	48
Issue number	6
DOIs	https://doi.org/10.1038/ng.3564
State	Published - Jun 1 2016

ASJC Scopus subject areas

Genetics

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Campbell, J. D., Alexandrov, A., Kim, J., Wala, J., Berger, A. H., Pedamallu, C. S., Shukla, S. A., Guo, G., Brooks, A. N., Murray, B. A., Imielinski, M., Hu, X., Ling, S., Akbani, R., Rosenberg, M., Cibulskis, C., Ramachandran, A., Collisson, E. A., Kwiatkowski, D. J., ... Meyerson, M. (2016). Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nature Genetics, 48(6), 607-616. https://doi.org/10.1038/ng.3564

Campbell, JD, Alexandrov, A, Kim, J, Wala, J, Berger, AH, Pedamallu, CS, Shukla, SA, Guo, G, Brooks, AN, Murray, BA, Imielinski, M, Hu, X, Ling, S, Akbani, R, Rosenberg, M, Cibulskis, C, Ramachandran, A, Collisson, EA, Kwiatkowski, DJ, Lawrence, MS, Weinstein, JN, Verhaak, RGW, Wu, CJ, Hammerman, PS, Cherniack, AD, Getz, G, Artyomov, MN, Schreiber, R, Govindan, R & Meyerson, M 2016, 'Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas', Nature Genetics, vol. 48, no. 6, pp. 607-616. https://doi.org/10.1038/ng.3564

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title = "Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas",

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.",

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

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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

PY - 2016/6/1

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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.

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

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