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.
Leary
Rebecca J
RJ
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.
Lin
Jimmy C
JC
Cummins
Jordan
J
Boca
Simina
S
Wood
Laura D
LD
Parsons
D Williams
DW
Jones
Siân
S
Sjöblom
Tobias
T
Park
Ben-Ho
BH
Parsons
Ramon
R
Willis
Joseph
J
Dawson
Dawn
D
Willson
James K V
JK
Nikolskaya
Tatiana
T
Nikolsky
Yuri
Y
Kopelovich
Levy
L
Papadopoulos
Nick
N
Pennacchio
Len A
LA
Wang
Tian-Li
TL
Markowitz
Sanford D
SD
Parmigiani
Giovanni
G
Kinzler
Kenneth W
KW
Vogelstein
Bert
B
Velculescu
Victor E
VE
D001943:Breast Neoplasms / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics*; D017353:Gene Deletion; D006720:Homozygote; D015398:Signal Transduction