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

被引：905

作者：

Campbell, Joshua D. ^{[1
,2
]}

Alexandrov, Anton ^{[3
,4
]}

Kim, Jaegil ^{[1
]}

Wala, Jeremiah ^{[1
,2
]}

Berger, Alice H. ^{[1
,2
]}

Pedamallu, Chandra Sekhar ^{[1
,2
]}

Shukla, Sachet A. ^{[1
,2
]}

Guo, Guangwu ^{[1
,2
]}

Brooks, Angela N. ^{[1
,2
]}

Murray, Bradley A. ^{[1
,2
]}

Imielinski, Marcin ^{[1
,2
,5
]}

Hu, Xin ^{[6
]}

Ling, Shiyun ^{[6
]}

Akbani, Rehan ^{[6
]}

Rosenberg, Mara ^{[1
]}

Cibulskis, Carrie ^{[1
]}

Ramachandran, Aruna ^{[1
,2
]}

Collisson, Eric A. ^{[7
]}

Kwiatkowski, David J. ^{[1
,8
]}

Lawrence, Michael S. ^{[1
]}

Weinstein, John N. ^{[6
]}

Verhaak, Roel G. W. ^{[6
]}

Wu, Catherine J. ^{[1
,2
]}

Hammerman, Peter S. ^{[1
,2
]}

Cherniack, Andrew D. ^{[1
,2
]}

Getz, Gad ^{[1
,9
]}

Artyomov, Maxim N. ^{[3
]}

Schreiber, Robert ^{[3
]}

Govindan, Ramaswamy ^{[10
]}

Meyerson, Matthew ^{[1
,2
,11
]}

机构：

[1] Eli & Edythe L Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[3] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA

[4] ITMO Univ, Comp Technol Lab, St Petersburg, Russia

[5] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[7] Univ Calif San Francisco, Dept Med, San Francisco, CA USA

[8] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA

[9] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[10] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[11] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

来源：

NATURE GENETICS | 2016年 / 48卷 / 06期

关键词：

MUTATIONAL PROCESSES; DRIVER MUTATIONS; CANCER; LANDSCAPE; KINASE; QUANTIFICATION; IDENTIFICATION; HETEROGENEITY; EXPRESSION; PREDICTION;

D O I：

10.1038/ng.3564

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：607 / +

页数：12

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