Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 28, 2011; 17(24): 2909-2923
Published online Jun 28, 2011. doi: 10.3748/wjg.v17.i24.2909
Genomic imbalances in esophageal carcinoma cell lines involve Wnt pathway genes
Jacqueline Brown, Hannelie Bothma, Robin Veale, Pascale Willem
Jacqueline Brown, Hannelie Bothma, Pascale Willem, National Health Laboratory Services and University of the Witwatersrand, York Rd, Parktown Johannesburg 2193, South Africa
Robin Veale, School of Molecular and Cell Biology, University of the Witwatersrand, Yale Rd, Johannesburg 2193, South Africa
Author contributions: Brown J performed most experiments, did the analysis and wrote this manuscript; Bothma H performed analysis of conventional cytogenetics; Veale R provided and cultured the cell lines; Willem P conceptualized the study, assisted with results analysis and wrote this manuscript.
Supported by The Cancer Association of South Africa, the National Health Laboratory Services Research Trust and the Medical Research council of South Africa
Correspondence to: Jacqueline Brown, MSc, National Health Laboratory Services and University of the Witwatersrand, York Rd, Parktown Johannesburg 2193, South Africa. jacqueline.brown@nhls.ac.za
Telephone: +27-11-4898575 Fax: +27-11-4898480
Received: October 7, 2010
Revised: October 30, 2010
Accepted: November 6, 2010
Published online: June 28, 2011
Abstract

AIM: To identify molecular markers shared across South African esophageal squamous cell carcinoma (ESCC) cell lines using cytogenetics, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism (SNP) array copy number analysis.

METHODS: We used conventional cytogenetics, FISH, and multicolor FISH to characterize the chromosomal rearrangements of five ESCC cell lines established in South Africa. The whole genome copy number profile was established from 250K SNP arrays, and data was analyzed with the CNAT 4.0 and GISTIC software.

RESULTS: We detected common translocation breakpoints involving chromosomes 1p11-12 and 3p11.2, the latter correlated with the deletion, or interruption of the EPHA3 gene. The most significant amplifications involved the following chromosomal regions and genes: 11q13.3 (CCND1, FGF3, FGF4, FGF19, MYEOV), 8q24.21(C-MYC, FAM84B), 11q22.1-q22.3 (BIRC2, BIRC3), 5p15.2 (CTNND2), 3q11.2-q12.2 (MINA) and 18p11.32 (TYMS, YES1). The significant deletions included 1p31.2-p31.1 (CTH, GADD45α, DIRAS3), 2q22.1 (LRP1B), 3p12.1-p14.2 (FHIT), 4q22.1-q32.1 (CASP6, SMAD1), 8p23.2-q11.1 (BNIP3L) and 18q21.1-q21.2 (SMAD4, DCC). The 3p11.2 translocation breakpoint was shared across four cell lines, supporting a role for genes involved at this site, in particular, the EPHA3 gene which has previously been reported to be deleted in ESCC.

CONCLUSION: The finding that a significant number of genes that were amplified (FGF3, FGF4, FGF19, CCND1 and C-MYC) or deleted (SFRP2 gene) are involved in the Wnt and fibroblast growth factor signaling pathways, suggests that these pathways may be activated in these cell lines.

Keywords: Esophagus; Cancer; Single nucleotide polymorphism arrays; Fluorescent in situ hybridization