SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

被引：798

作者：

Bass, Adam J. ^{[1
,2
,3
,4
]}

Watanabe, Hideo ^{[1
,3
,4
]}

Mermel, Craig H. ^{[1
,3
,4
]}

Yu, Soyoung ^{[1
,3
]}

Perner, Sven ^{[5
,6
]}

Verhaak, Roel G. ^{[1
,3
,4
]}

Kim, So Young ^{[1
,3
]}

Wardwell, Leslie ^{[1
,3
]}

Tamayo, Pablo ^{[4
]}

Gat-Viks, Irit ^{[4
]}

Ramos, Alex H. ^{[1
,3
,4
]}

Woo, Michele S. ^{[1
,3
,4
]}

Weir, Barbara A. ^{[1
,3
,4
]}

Getz, Gad ^{[4
]}

Beroukhim, Rameen ^{[1
,2
,3
,4
]}

O'Kelly, Michael ^{[4
]}

Dutt, Amit ^{[1
,3
,4
]}

Rozenblatt-Rosen, Orit ^{[1
,3
]}

Dziunycz, Piotr ^{[1
]}

Komisarof, Justin ^{[1
]}

Chirieac, Lucian R. ^{[7
]}

LaFargue, Christopher J. ^{[5
]}

Scheble, Veit ^{[6
]}

Wilbertz, Theresia ^{[6
]}

Ma, Changqing ^{[8
]}

Rao, Shilpa ^{[8
]}

Nakagawa, Hiroshi ^{[8
,9
]}

Stairs, Douglas B. ^{[8
,9
]}

Lin, Lin ^{[10
]}

Giordano, Thomas J. ^{[11
]}

Wagner, Patrick ^{[5
]}

Minna, John D. ^{[12
]}

Gazdar, Adi F. ^{[12
]}

Zhu, Chang Qi ^{[13
,14
]}

Brose, Marcia S. ^{[8
,15
]}

Cecconello, Ivan ^{[16
]}

Ribeiro, Ulysses, Jr. ^{[16
]}

Marie, Suely K. ^{[16
]}

Dahl, Olav ^{[17
]}

Shivdasani, Ramesh A. ^{[1
,2
]}

Tsao, Ming-Sound ^{[13
,14
]}

Rubin, Mark A. ^{[5
]}

Wong, Kwok K. ^{[1
,2
]}

Regev, Aviv ^{[4
]}

Hahn, William C. ^{[1
,2
,3
,4
]}

Beer, David G. ^{[10
]}

Rustgi, Anil K. ^{[8
,9
,18
]}

Meyerson, Matthew ^{[1
,3
,4
,7
]}

机构：

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

[2] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[3] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

[4] Broad Inst, Cambridge, MA USA

[5] Cornell Univ, Dept Pathol, Weill Med Coll, New York, NY 10021 USA

[6] Univ Tubingen Hosp, Inst Pathol, Ctr Comprehens Canc, Tubingen, Germany

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

[8] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[9] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[10] Univ Michigan, Dept Surg, Thorac Surg Sect, Ann Arbor, MI 48109 USA

[11] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[12] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[13] Univ Hlth Network, Toronto, ON, Canada

[14] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada

[15] Univ Penn, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA

[16] Univ Sao Paulo, Sch Med, Bauru, SP, Brazil

[17] Univ Bergen, Sect Oncol, Bergen, Norway

[18] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 11期

关键词：

GENE; EXPRESSION; CANCER; REVEALS; ADENOCARCINOMAS; DIFFERENTIATION; IDENTIFICATION; AMPLIFICATION; DEPENDENCY; CONSISTENT;

D O I：

10.1038/ng.465

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Lineage-survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development(1,2). Here we show that a peak of genomic amplification on chromosome 3q26.33 found in squamous cell carcinomas (SCCs) of the lung and esophagus contains the transcription factor gene SOX2, which is mutated in hereditary human esophageal malformations(3), is necessary for normal esophageal squamous development(4), promotes differentiation and proliferation of basal tracheal cells(5) and cooperates in induction of pluripotent stem cells(6-8). SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 here cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.

引用

页码：1238 / U105

页数：7

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