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John Harmon

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Hypermethylation of the GATA gene family in esophageal cancer.

MingZhou Guo; Michael G House; Yoshimitsu Akiyama; Yu Qi; Domenico Capagna; John Harmon; Stephen B Baylin; Malcolm V Brock; James G Herman (Profiled Authors: Malcolm Brock; Mingzhou Guo; John Harmon; James Herman; Stephen Baylin)

Cancer Biology Program, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231-1000, USA.
International journal of cancer. Journal international du cancer 2006;119(9):2078-83.

Abstract

The GATA family of transcription factors promotes the normal development of the gastrointestinal tract during embryogenesis and determines tissue differentiation in adult gut epithelium. Loss of GATA-4 and GATA-5 has been reported in human gastric and colon cancer. We examined GATA-4,-5 and -6 gene expression in established esophageal squamous cancer cell lines and the relationship to DNA methylation in the promoter region of these genes. GATA-4 and GATA-5 expression was absent in most esophageal cancer cell lines, but was restored upon treatment with the demethylating agent 5-aza-2'-deoxycytidine. For each of the cell lines without detectable GATA gene expression, aberrant methylation of the promoter region CpG-island was detected by methylation specific PCR. We confirmed these results with genomic bisulfite sequencing. GATA-6 expression was found in each of the cell lines. GATA-4/-5 promoter methylation was not detected in normal esophageal mucosa, but GATA-4 methylation was present in 27 of 44 (61%) squamous carcinomas and 31 of 44 (71%) adenocarcinoma of the esophagus, while GATA-5 methylation was present in 14 of 44 (32%) squamous carcinomas and 24 of 44 (55%) adenocarcinoma of the esophagus. Our studies demonstrate frequent silencing of GATA-4 and GATA-5, but not GATA-6, in human esophageal neoplasia associated with gene promoter hypermethylation.

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