Genome-wide copy number analysis in esophageal adenocarcinoma using high-density single-nucleotide polymorphism arrays

Nancarrow, D.J., Handoko, H. Y., Smithers, B.M., Gotley, D. C., Drew, P.A., Watson, D.I., Clouston, A. D., Hayward, N. and Whiteman, D. C. (2008) Genome-wide copy number analysis in esophageal adenocarcinoma using high-density single-nucleotide polymorphism arrays. Cancer Research, 68 11: 4163-4172. doi:10.1158/0008-5472.CAN-07-6710

Author Nancarrow, D.J.
Handoko, H. Y.
Smithers, B.M.
Gotley, D. C.
Drew, P.A.
Watson, D.I.
Clouston, A. D.
Hayward, N.
Whiteman, D. C.
Title Genome-wide copy number analysis in esophageal adenocarcinoma using high-density single-nucleotide polymorphism arrays
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
Publication date 2008-06-01
Year available 2008
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-07-6710
Volume 68
Issue 11
Start page 4163
End page 4172
Total pages 10
Editor F.J. Rauscher
Place of publication Philadelphia, PA, U.S.
Publisher American Association for Cancer Research (AACR)
Collection year 2009
Language eng
Subject C1
920102 Cancer and Related Disorders
111203 Cancer Genetics
1112 Oncology and Carcinogenesis
Formatted abstract
We applied whole-genome single-nucleotide polymorphism arrays to define a comprehensive genetic profile of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies based on loss of heterozygosity (LOH) and DNA copy number changes. Alterations were common, averaging 97 (range, 23-208) per tumor. LOH and gains averaged 33 (range, 3-83) and 31 (range, 11-73) per tumor, respectively. Copy neutral LOH events averaged 27 (range, 7-57) per EAC. We noted 126 homozygous deletions (HD) across the EAC panel (range, 0-11 in individual tumors). Frequent HDs within FHIT (17 of 23), WWOX (8 of 23), and DMD (6 of 23) suggest a role for common fragile sites or genomic instability in EAC etiology. HDs were also noted for known tumor suppressor genes (TSG), including CDKN2A, CDKN2B, SMAD4, and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs. All tumors showed LOH for most of chromosome 17p, suggesting that TSGs other than TP53 may be targeted. Frequent gains were noted around MYC (13 of 23), BCL9 (12 of 23), CTAGE1 (14 of 23), and ZNF217 (12 of 23). Thus, we have confirmed previous reports indicating frequent changes to FHIT, CDKN2A, TP53, and MYC in EAC and identified additional genes of interest. Meta-analysis of previous genome-wide EAC studies together with the data presented here highlighted consistent regions of gain on 8q, 18q, and 20q and multiple LOH regions on 4q, 5q, 17p, and 18q, suggesting that more than one gene may be targeted on each of these chromosome arms. The focal gains and deletions documented here are a step toward identifying the key genes involved in EAC development.
©2008 American Association for Cancer Research.
Keyword Chromosome 17p
Chromosome 18q
Chromosome 20q
Chromosome 4q
Chromosome 5q
Chromosome 8q
Esophageal adenocarcinoma
Gene deletion
Gene identification
Genome analysis
Single nucleotide polymorphism
Tumor suppressor gene
Chromosome map
DNA microarray
References adult; aged; article; chromosome 17p; chromosome 18q; chromosome 20q; chromosome 4q; chromosome 5q; chromosome 8q; clinical article; esophageal adenocarcinoma; female; gene deletion; gene identification; gene number; genome analysis; genomic instability; heterozygosity loss; human; male; priority journal; single nucleotide polymorphism; tumor biopsy; tumor suppressor gene; adenocarcinoma; chromosome map; DNA microarray; esophagus tumor; gene expression profiling; genetics; genome
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 59 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 14 Apr 2009, 16:50:05 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital