Multiple forms of genetic instability within a 2-Mb chromosomal segment of 3q26.3–q27 are associated with development of esophageal adenocarcinoma
Lin, Lin; Wang, Zhuwen; Prescott, Michael S.; van Dekken, Herman; Thomas, Dafydd G.; Giordano, Thomas J.; Chang, Andrew C.; Orringer, Mark B.; Gruber, Stephen B.; Moran, John V.; Glover, Thomas W.; Beer, David G.
2006-04
Citation
Lin, Lin; Wang, Zhuwen; Prescott, Michael S.; van Dekken, Herman; Thomas, Dafydd G.; Giordano, Thomas J.; Chang, Andrew C.; Orringer, Mark B.; Gruber, Stephen B.; Moran, John V.; Glover, Thomas W.; Beer, David G. (2006). "Multiple forms of genetic instability within a 2-Mb chromosomal segment of 3q26.3–q27 are associated with development of esophageal adenocarcinoma." Genes, Chromosomes and Cancer 45(4): 319-331. <http://hdl.handle.net/2027.42/50630>
Abstract
Gene amplification is one of the mechanisms to activate oncogenes in many cancers, including esophageal adenocarcinoma (EA). In the present study, we used two-dimensional restriction landmark genome scanning to clone a Not I/ Dpn II fragment that showed increased genomic dosage in 1 of 44 EAs analyzed. This fragment maps to 3q26.3–q27, and subsequent experiments identified two intrachromosomal amplicons within a 10-Mb DNA segment in 7 of 75 (9%) EAs. The distal amplified-core region maps centromeric to the PIK3CA locus, and a microsatellite ( D3S1754 ) within this region exhibited significant instability (MSI), in stark contrast to the genomewide microsatellite stability found in EA. D3S1754-MSI arises in premalignant Barrett's dysplastic cells and preceded amplification of the nascent MSI allele in the corresponding EA. Seven ESTs within the amplified-core were overexpressed in amplicon-containing EAs. One of these, EST AW513672 , represents a chimeric transcript that initiated from an antisense promoter sequence in the 5′UTR of a full-length LINE-1 element (L1-5′ASP). Similar chimeric transcripts encoding portions of the MET oncogene and the BCAS3 gene also were overexpressed in EAs, suggesting that L1-5′ASP activation may occur at a broad level in primary EAs. Thus, the fine dissection of a 2-Mb amplified DNA segment in 3q26.3–q27 in EA revealed multiple genetic alterations that had occurred sequentially and/or concurrently during EA development. This article has supplementary material, available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat . © 2005 Wiley-Liss, Inc.Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
1045-2257 1098-2264
Other DOIs
PMID
16320248
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16320248&dopt=citationMetadata
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