Silence of chromosomal amplifications in colon cancer.
Oncogene activation by gene amplification is a major pathogenetic mechanism in human cancer. Using comparative genomic hybridization, we determined that metastatic human colon cancers commonly acquire numerous extra copies of chromosome arms 7p, 8q, 13q, and 20q. We then examined the consequence of these amplifications on gene expression using DNA microarrays. Of 55,000 transcripts profiled, 2,146 were determined to map to one of the four common colon cancer amplicons and to also be expressed in normal or malignant colon tissues. Of these, only 81 transcripts (3.8%) demonstrated a 2-fold increase over normal expression among cancers bearing the corresponding chromosomal amplification. Chromosomal amplifications are common in colon cancer metastasis, but increased expression of genes within these amplicons is rare.
Platzer
Petra
P
Howard Hughes Medical Institute, Cleveland, Ohio 44106, USA.
Upender
Madhvi B
MB
Wilson
Keith
K
Willis
Joseph
J
Lutterbaugh
James
J
Nosrati
Arman
A
Willson
James K V
JK
Mack
David
D
Ried
Thomas
T
Markowitz
Sanford
S
D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation