A Genome-Wide Screen for Microdeletions Reveals Disruption of Polarity Complex Genes in Diverse Human Cancers

被引:67
作者
Rothenberg, S. Michael [1 ,3 ,4 ]
Mohapatra, Gayatry [1 ,5 ]
Rivera, Miguel N. [1 ,3 ,5 ]
Winokur, Daniel [1 ]
Greninger, Patricia [1 ,2 ]
Nitta, Mai [1 ,5 ]
Sadow, Peter M. [5 ]
Sooriyakumar, Gaya [1 ]
Brannigan, Brian W. [1 ]
Ulman, Matthew J. [1 ]
Perera, Rushika M. [1 ]
Wang, Rui [6 ]
Tam, Angela [1 ,2 ]
Ma, Xiao-Jun [7 ]
Erlander, Mark [7 ]
Sgroi, Dennis C. [1 ,5 ]
Rocco, James W. [1 ]
Lingen, Mark W. [8 ]
Cohen, Ezra E. W. [9 ]
Louis, David N. [1 ,5 ]
Settleman, Jeffrey [1 ,2 ]
Haber, Daniel A. [1 ,3 ]
机构
[1] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA
[2] Harvard Univ, Ctr Mol Therapeut, Sch Med, Charlestown, MA USA
[3] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA
[4] Massachusetts Gen Hosp, Ctr Head & Neck Canc, Boston, MA 02114 USA
[5] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA
[6] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA
[7] Biotheranostics, San Diego, CA USA
[8] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA
[9] Univ Chicago, Dept Med, Chicago, IL 60637 USA
关键词
REPRESENTATIONAL DIFFERENCE ANALYSIS; COPY-NUMBER; CELL POLARITY; ARRAY; HYBRIDIZATION; CARCINOMA; MICROARRAYS; EXPRESSION; DROSOPHILA; PATTERNS;
D O I
10.1158/0008-5472.CAN-09-3458
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In a genome-wide screen of 684 cancer cell lines, we identified homozygous intragenic microdeletions involving genes encoding components of the apical-basal cell polarity complexes. Among these, PARD3 is disrupted in cell lines and primary tumors from squamous carcinomas and glioblastomas. Reconstituting PARD3 expression in both cell types restores tight junctions and retards contact-dependent proliferation. Searching specifically for small intragenic microdeletions using high-resolution genomic arrays may be complementary to other genomic deletion screens and resequencing efforts in identifying new tumor suppressor genes. Cancer Res; 70(6); 2158-64. (C) 2010 AACR.
引用
收藏
页码:2158 / 2164
页数:7
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