Genome-wide catalogue of chromosomal aberrations in Barrett's esophagus and esophageal adenocarcinoma: A high-density single nucleotide polymorphism array analysis

Jian Gu, Jaffer A. Ajani, Ernest T. Hawk, Yuanqing Ye, Jeffrey H. Lee, Manoop S. Bhutani, Wayne L. Hofstetter, Stephen G. Swisher, Kenneth K. Wang, Xifeng Wu

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

To better understand the molecular mechanisms behind esophageal adenocarcinoma (EAC) tumorigenesis, we used high-density single nucleotide polymorphism arrays to profile chromosomal aberrations at each of the four sequential progression stages, Barrett's metaplasia (BM), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC, in 101 patients. We observed a significant trend toward increasing loss of chromosomes with higher progression stage. For BM, LGD, HGD, and EAC, respectively, the average numbers of chromosome arms with loss per sample were 0.30, 3.21, 7.70, and 11.90 (P for trend = 4.82 × 10-7), and the mean percentages of single nucleotide polymorphisms with allele loss were 0.1%, 1.8%, 6.6%, and 17.2% (P for trend = 2.64 × 10-6). In LGD, loss of 3p14.2 (68.4%) and 16q23.1 (47.4%) was limited to narrow regions within the FHIT (3p14.2) and WWOX (16q23.1) genes, whereas loss of 9p21 (68.4%) occurred in larger regions. A significant increase in the loss of other chromosomal regions was seen in HGD and EAC. Loss of 17p (47.6%) was one of the most frequent events in EAC. Many recurrent small regions of chromosomal loss disrupted single genes, including FHIT, WWOX, RUNX1, KIF26B, MGC48628, PDE4D, C20orf133, GMDS, DMD, and PARK2, most of which are common fragile site regions in the human genome. However, RUNX1 at 21q22 seemed to be a potential tumor suppressor gene in EAC. Amplifications were less frequent than losses and mostly occurred in EAC. 8q24 (containing Myc) and 8p23.1 (containing CTSB) were the two most frequently amplified regions. In addition, a significant trend toward increasing amplification was associated with higher progression stage.

Original languageEnglish (US)
Pages (from-to)1176-1186
Number of pages11
JournalCancer Prevention Research
Volume3
Issue number9
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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