Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 125, Issue 10, Pages 2349-2359Publisher
WILEY
DOI: 10.1002/ijc.24620
Keywords
esophageal adenocarcinoma; SNP-chip; copy-number-neutral LOH; BNV2
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Funding
- NCI NIH HHS [CA 84986, CA106763, R21 CA106763, R01 CA001808, U01 CA084986, CA85069, U01 CA085069, U01 CA085069-10S1, CA01808] Funding Source: Medline
- NIDDK NIH HHS [R01 DK087454] Funding Source: Medline
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Barrett's esophagus ( BE) is metaplastic condition caused by chronic gastroesophageal reflux which represents in early step in file development of esophageal adenocarcinoma (EAC). Single-nucleotide polymorphism microarray (SNP-chip). analysis is I novel. precise. high-throughput approach to examine genomic alterations ill neoplasia. Using 250K SNP-chips, we examined the neoplastic progression or BE to EAC, studying 11 matched sample sets: 6 sets of normal esophagus (NE), BE. and EAC, 4 of NE in(] BE and 1 of NE and EAC. Six (60%) of 10 total HE samples and 4 (57%) of 7 total EAC samples exhibited I or more genomic abnormalities comprising deletions, duplications, amplifications and copy-number-neutral loss of heterozygosity (CNN-LOH). Several shared abnormalities were identified, including chromosome 9p CNN-LOH [2 BE samples (20%)]. deletion of CDKA12A [4 BE samples (40%)] amplification of 17q12-21.2 involving the ERBB2, RARA and T0P2A genes [3.1 Mb, 2 EAC (29%)]. Infereslingly. 1 BE sample contained I lioniozygous deletion spanning 9p22.3-p22.2 (1.2 Mb): this region harbors only I known gene, basonuclin 2 (BNC2). Real-time PCR analysis confirmed the deletion of this gene and decreased the expression of BNC2 mRNA in (lie BE sample. Furthermore, transfection and stable expression of BNC2 caused growth arrest of OE33 EAC cells, suggesting that BNC2 functions as a funior suppressor gene in file esophagus and that deletion of this gene occurs during the development of EAC. Thus, this SNP-chip analysis has identified several early Cytogenetic events and novel candidate cancer-relaled genes that are potentially involved in the evolution of BE to EAC. (C) 2009 UICC
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