High-resolution characterization of the pancreatic adenocarcinoma genome Journal Article
| Authors: | Aguirre, A. J.; Brennan, C.; Bailey, G.; Sinha, R.; Feng, B.; Leo, C.; Zhang, Y.; Zhang, J.; Gans, J. D.; Bardeesy, N.; Cauwels, C.; Cordon-Cardo, C.; Redston, M. S.; DePinho, R. A.; Chin, L. |
| Article Title: | High-resolution characterization of the pancreatic adenocarcinoma genome |
| Abstract: | 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. |
| Keywords: | human tissue; human cell; gene deletion; pancreatic neoplasms; adenocarcinoma; animals; gene amplification; gene expression; gene expression profiling; computational biology; cancer cell culture; cell line, tumor; carcinogenesis; rna; cancer genetics; gene number; oncogene; tumor suppressor gene; dna; messenger rna; oligonucleotide array sequence analysis; homozygote; gene loss; pancreas adenocarcinoma; genome; dna microarray; cyclin-dependent kinase inhibitor p16; array comparative genomic hybridization; gene dosage; nucleic acid hybridization; tumor growth; sequence homology; information science; comparative genomic hybridization; chromosomes; complementary dna; chromosomes, human, pair 17; expression profile; humans; human; priority journal; article; minimal common region |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 101 |
| Issue: | 24 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2004-06-15 |
| Start Page: | 9067 |
| End Page: | 9072 |
| Language: | English |
| DOI: | 10.1073/pnas.0402932101 |
| PROVIDER: | scopus |
| PMCID: | PMC428474 |
| PUBMED: | 15199222 |
| DOI/URL: | |
| Notes: | Proc. Natl. Acad. Sci. U. S. A. -- Cited By (since 1996):168 -- Export Date: 16 June 2014 -- CODEN: PNASA -- Source: Scopus |
