Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers.
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.
The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
Rebecca J
RJ
Leary
Jimmy C
JC
Lin
Jordan
J
Cummins
Simina
S
Boca
Laura D
LD
Wood
D Williams
DW
Parsons
Siân
S
Jones
Tobias
T
Sjöblom
Ben-Ho
BH
Park
Ramon
R
Parsons
Joseph
J
Willis
Dawn
D
Dawson
James K V
JK
Willson
Tatiana
T
Nikolskaya
Yuri
Y
Nikolsky
Levy
L
Kopelovich
Nick
N
Papadopoulos
Len A
LA
Pennacchio
Tian-Li
TL
Wang
Sanford D
SD
Markowitz
Giovanni
G
Parmigiani
Kenneth W
KW
Kinzler
Bert
B
Vogelstein
Victor E
VE
Velculescu
D001943:Breast Neoplasms / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics*; D017353:Gene Deletion; D006720:Homozygote; D015398:Signal Transduction