Comprehensive genomic characterization of squamous cell lung cancers

被引：3173

作者：

Hammerman, Peter S. ^{[2
]}

Lawrence, Michael S.

Voet, Douglas

Jing, Rui

Cibulskis, Kristian

Sivachenko, Andrey ^{[1
]}

Stojanov, Petar

McKenna, Aaron ^{[1
]}

Lander, Eric S. ^{[3
,4
]}

Gabriel, Stacey ^{[5
]}

Getz, Gad ^{[5
]}

Sougnez, Carrie ^{[4
,5
]}

Imielinski, Marcin ^{[6
]}

Helman, Elena

Hernandez, Bryan

Pho, Nam H.

Meyerson, Matthew ^{[2
,6
]}

Chu, Andy ^{[7
]}

Chun, Hye-Jung E. ^{[7
]}

Mungall, Andrew J. ^{[7
]}

Pleasance, Erin ^{[7
]}

Robertson, A. Gordon ^{[7
]}

Sipahimalani, Payal ^{[7
]}

Stoll, Dominik ^{[7
]}

Balasundaram, Miruna ^{[7
]}

Birol, Inanc ^{[7
]}

Butterfield, Yaron S. N.

Chuah, Eric ^{[7
]}

Coope, Robin J. N.

Corbett, Richard

Dhalla, Noreen

Guin, Ranabir ^{[7
]}

Hirst, Anhe Carrie ^{[7
]}

Hirst, Martin ^{[7
]}

Holt, Robert A.

Lee, Darlene ^{[7
]}

Li, Haiyan I. ^{[7
]}

Mayo, Michael ^{[7
]}

Moore, Richard A.

Mungall, Karen ^{[7
]}

Nip, Ka Ming ^{[7
]}

Olshen, Adam ^{[8
,9
]}

Schein, Jacqueline E. ^{[7
]}

Slobodan, Jared R. ^{[7
]}

Tam, Angela

Thiessen, Nina ^{[7
]}

Varhol, Richard

Zeng, Thomas

Zhao, Yongjun

Jones, Steven J. M.

机构：

[1] MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[3] MIT, Dept Biol, Cambridge, MA 02142 USA

[4] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA

[5] Harvard Univ, Genet Anal Platform, Cambridge, MA 02142 USA

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

[7] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z, Canada

[8] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[9] Dana Farber Canc Inst, Boston, MA 02115 USA

[10] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Dept Genom Med, Houston, TX 77030 USA

[11] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[12] Harvard Univ, Ctr Biomed Informat, Sch Med, Boston, MA 02115 USA

[13] Childrens Hosp, Informat Program, Boston, MA 02115 USA

[14] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA

[15] Mem Sloan Kettering Canc Ctr, Dept Mol Oncol, New York, NY 10065 USA

[16] Mem Sloan Kettering Canc Ctr, Dept Pathol & Human Oncol, New York, NY 10065 USA

[17] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

[18] Univ N Carolina, Inst Pharmacogenet & Individualized Therapy, Chapel Hill, NC 27599 USA

[19] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[20] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA

[21] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[22] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA

[23] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA

[24] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA

[25] Univ Kentucky, Dept Comp Sci, Lexington, KY 40506 USA

[26] Univ N Carolina, Dept Internal Med, Div Med Oncol, Chapel Hill, NC 27599 USA

[27] Johns Hopkins Univ, Canc Biol Div, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA

[28] Univ So Calif, Calif Epigenome Ctr, Los Angeles, CA 90033 USA

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

[30] Univ Texas MD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA

[31] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[32] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA

[33] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA

[34] Buck Inst Age Res, Novato, CA 94945 USA

[35] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA

[36] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27599 USA

[37] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[38] Baylor Coll Med, Dan L Duncan Canc Ctr, Div Biostat, Houston, TX 77030 USA

[39] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[40] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA

[41] Roswell Pk Canc Inst, Dept Pathol, Buffalo, NY 14263 USA

[42] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA

[43] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA

[44] Univ N Carolina, Dept Pathol, Med Ctr, Chapel Hill, NC 27599 USA

[45] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA

[46] Penrose St Francis Hlth Syst, Dept Pathol, Colorado Springs, CO 80907 USA

[47] Ontario Canc Inst, Dept Pathol & Med Biophys, Toronto, ON M5G 2MY, Canada

[48] Princess Margaret Hosp, Toronto, ON M5G 2MY, Canada

[49] Int Genom Consortium, Phoenix, AZ 85004 USA

[50] Washington Univ, Dept Med, Div Oncol, Sch Med, St Louis, MO 63110 USA

来源：

NATURE | 2012年 / 489卷 / 7417期

基金：

美国国家科学基金会;

关键词：

COPY-NUMBER ALTERATION; THERAPEUTIC TARGET; MUTATIONS; GENE; CARCINOMA; AMPLIFICATION; SENSITIVITY; LANDSCAPE; GEFITINIB; ONCOGENE;

D O I：

10.1038/nature11404

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

引用

页码：519 / 525

页数：7

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共 46 条

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Jasser, Samar A. ;

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