MAL hypermethylation is a tissue-specific event that correlates with MAL mRNA expression in esophageal carcinoma
نویسندگان
چکیده
MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2'-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors.
منابع مشابه
Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy.
Dysregulation of MAL (myelin and lymphocyte protein) has been implicated in several malignancies including esophageal, ovarian, and cervical cancers. The MAL protein functions in apical transport in polarized epithelial cells; therefore, its disruption may lead to loss of organized polarity characteristic of most solid malignancies. Bisulfite sequencing of the MAL promoter CpG island revealed h...
متن کاملAberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer
Genome-wide DNA hypomethylation and gene hypermethylation play important roles in instability and carcino-genesis. Methylation in long interspersed nucleotide element 1 (LINE-1) is a good indicator of the global DNA methylation level within a cell. Slit homolog 2 (SLIT2), myelin and lymphocyte protein gene (MAL) and insulin-like growth factor bind...
متن کاملPromoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors.
Although the CDH13 gene has been shown to undergo epigenetic silencing by promoter methylation in many types of tumors, hypermethylation of this gene in Barrett's-associated esophageal adenocarcinogenesis has not been studied. Two hundred fifty-nine human esophageal tissues were therefore examined for CDH13 promoter hypermethylation by real-time methylation-specific PCR. CDH13 hypermethylation ...
متن کاملRepression of MAL tumour suppressor activity by promoter methylation during cervical carcinogenesis.
We recently identified MAL (T-lymphocyte maturation associated protein) as the most down-regulated gene in cervical oncogenesis. Here, we examined the mechanism underlying MAL silencing, its functional role in cervical carcinogenesis, and the relevance of detecting MAL alterations for risk assessment of hrHPV-positive women. MAL mRNA expression and promoter methylation were analysed in primary ...
متن کاملTwo Steps Methylation Specific PCR for Assessment of APC Promoter Methylation in Gastric Adenocarcinoma
Gastric Cancer (GC) is the second most common cancer in the world and a leading cause of cancer-related mortality. Methylation of promoter CpG islands (CGIs) belonging to tumor suppressor genes causes transcriptional silencing of their corresponding genes leading to carcinogenesis and other disorders. Adenomatous Polyposis Coli (APC) a tumor suppressor gene is inactivated by methylation of prom...
متن کامل