Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers

被引：221

作者：

Leary, Rebecca J. ^{[1
,2
]}

Lin, Jimmy C. ^{[1
,2
]}

Cummins, Jordan ^{[1
,2
]}

Boca, Simina ^{[1
,2
,3
,4
]}

Wood, Laura D. ^{[1
,2
]}

Parsons, D. Williams ^{[1
,2
]}

Jones, Sian ^{[1
,2
]}

Sjoeblom, Tobias ^{[1
,2
]}

Park, Ben-Ho ^{[5
]}

Parsons, Ramon ^{[6
]}

Willis, Joseph ^{[7
,8
,9
,10
]}

Dawson, Dawn ^{[7
,8
,9
,10
]}

Willson, James K. V. ^{[11
]}

Nikolskaya, Tatiana ^{[12
,13
]}

Nikolsky, Yuri ^{[13
]}

Kopelovich, Levy ^{[14
]}

Papadopoulos, Nick ^{[1
,2
]}

Pennacchio, Len A. ^{[15
]}

Wang, Tian-Li ^{[1
,2
]}

Markowitz, Sanford D. ^{[7
,8
,9
,10
]}

Parmigiani, Giovanni ^{[1
,2
,3
,4
]}

Kinzler, Kenneth W. ^{[1
,2
]}

Vogelstein, Bert ^{[1
,2
]}

Velculescu, Victor E. ^{[1
,2
]}

机构：

[1] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA

[2] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA

[3] Johns Hopkins Kimmel Canc Ctr, Dept Bioinformat, Baltimore, MD 21231 USA

[4] Johns Hopkins Kimmel Canc Ctr, Dept Pathol, Baltimore, MD 21231 USA

[5] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA

[6] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA

[7] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA

[8] Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA

[9] Univ Hosp Cleveland, Cleveland, OH 44106 USA

[10] Howard Hughes Med Inst, Cleveland, OH 44106 USA

[11] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA

[12] NI Vavilov Gen Genet Res Inst, Moscow 117809, Russia

[13] GeneGo Inc, St Joseph, MI 49085 USA

[14] NCI, Canc Prevent Div, Bethesda, MD 20892 USA

[15] Joint Genome Inst, Dept Energy, Walnut Creek, CA 94598 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 42期

基金：

美国国家卫生研究院;

关键词：

amplification; copy number changes; Digital Karyotyping; high-density SNP arrays; homozygous deletion;

D O I：

10.1073/pnas.0808041105

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：

07 ; 0710 ; 09 ;

摘要：

we have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the number of genes altered by major copy number changes, deletion of all copies or amplification to at least 12 copies per cell, averaged 17 per tumor. We have integrated these data with previous mutation analyses of the Reference Sequence genes in these same tumor types and have identified genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations included those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that could prove useful for cancer diagnosis and therapy.

引用

页码：16224 / 16229

页数：6

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