Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression

McRonald, FE, Liloglou, T ORCID: 0000-0003-0460-1404, Xinarianos, G, Hill, L, Rowbottom, L, Langan, JE, Ellis, A, Shaw, JM, Field, JK ORCID: 0000-0003-3951-6365 and Risk, JM ORCID: 0000-0002-8770-7783 (2006) Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression. HUMAN MOLECULAR GENETICS, 15 (8). pp. 1271-1277.

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Abstract

Tylosis (focal non-epidermolytic palmoplantar keratoderma) is an autosomal dominant skin disorder that is associated with the early onset of squamous cell oesophageal cancer (SCOC) in three families. Our previous linkage and haplotype analyses have mapped the tylosis with oesophageal cancer (TOC) locus to a 42.5 kb region on chromosome 17q25 that has also been implicated in the aetiology of sporadically occurring SCOC from a number of different geographical populations. Oesophageal cancer is one of the 10 leading causes of cancer mortality worldwide. No inherited disease-causing mutations have been identified in the genes located in the 42.5 kb minimal region. We now show that cytoglobin gene expression in oesophageal biopsies from tylotic patients is dramatically reduced by approximately 70% compared with normal oesophagus. Furthermore, both alleles are equally repressed. Given the autosomal dominant nature of the disease, these results exclude haploinsufficiency as a mechanism of the disease and instead suggest a novel trans-allele interaction. We also show that the promoter is hypermethylated in sporadic oesophageal cancer samples: this may constitute the 'second hit' of a gene previously implicated in this disease by allelic imbalance studies.

Item Type:	Article
Additional Information:	030DK Times Cited:15 Cited References Count:29## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords:	Cell Line, Tumor, Chromosomes, Human, Pair 17, Humans, Esophageal Neoplasms, Keratoderma, Palmoplantar, Diffuse, Globins, Gene Expression Profiling, Sequence Analysis, DNA, Down-Regulation, Allelic Imbalance, Female, Male, Cytoglobin
Depositing User:	Symplectic Admin
Date Deposited:	30 Sep 2015 08:42
Last Modified:	16 Dec 2022 12:31
DOI:	10.1093/hmg/ddl042
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/2028893

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• Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression. (deposited 30 Sep 2015 08:42) [Currently Displayed]