High-resolution characterization of the pancreatic adenocarcinoma genome.
The pancreatic adenocarcinoma genome harbors multiple amplifications and deletions, pointing to the existence of numerous oncogenes and tumor suppressor genes driving the genesis and progression of this lethal cancer. Here, array comparative genomic hybridization on a cDNA microarray platform and informatics tools have been used to define the copy number alterations in a panel of 24 pancreatic adenocarcinoma cell lines and 13 primary tumor specimens. This high-resolution genomic analysis has identified all known regional gains and losses as well as many previously uncharacterized highly recurrent copy number alterations. A systematic prioritization scheme has selected 64 focal minimal common regions (MCRs) of recurrent copy number change. These MCRs possess a median size of 2.7 megabases (Mb), with 21 (33%) MCRs spanning 1 Mb or less (median of 0.33 Mb) and possessing an average of 15 annotated genes. Furthermore, complementary expression profile analysis of a significant fraction of the genes residing within these 64 prioritized MCRs has enabled the identification of a subset of candidates with statistically significant association between gene dosage and mRNA expression. Thus, the integration of DNA and RNA profiles provides a highly productive entry point for the discovery of genes involved in the pathogenesis of pancreatic adenocarcinoma.
Aguirre
Andrew J
AJ
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Brennan
Cameron
C
Bailey
Gerald
G
Sinha
Raktim
R
Feng
Bin
B
Leo
Christopher
C
Zhang
Yunyu
Y
Zhang
Jean
J
Gans
Joseph D
JD
Bardeesy
Nabeel
N
Cauwels
Craig
C
Cordon-Cardo
Carlos
C
Redston
Mark S
MS
DePinho
Ronald A
RA
Chin
Lynda
L
D000230:Adenocarcinoma / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D002875:Chromosomes / Q000235:genetics; D002886:Chromosomes, Human, Pair 17; D019295:Computational Biology / Q000379:methods; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage; D015870:Gene Expression; D016678:Genome; D006720:Homozygote; D006801:Humans; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics*
D019941:Cyclin-Dependent Kinase Inhibitor p16