Downregulation of DLC-1 Gene by Promoter Methylation during Primary Colorectal Cancer Progression

الملخص EN

Purpose.

DLC-1 is a tumor suppressor gene frequently silenced in human cancers.

However, the pathogenicity of DLC-1 epigenetic silencing in the mucosa-adenoma-carcinoma transformation process of colorectal cancer (CRC) has not been studied.

Methods.

Promoter methylation status of DLC-1 was evaluated in 4 human CRC cell lines, 48 normal mucosa, 57 adenomas, and 80 CRC tissues with methylation-sensitive high-resolution melting analysis (MS-HRMA), while the mRNA expression was examined by qPCR.

HRMA was utilized to detect the KRAS codon 12, 13 and BRAF V600Emutations.

Results.

Partial (1%–10%) and extensive (10%–100%) DLC-1 promoter methylations were observed in 10% and 0% of normal mucosa, 46% and 14% of adenomas, and 60% and 36% of CRCs, respectively.

The promoter methylation of DLC-1 was related with the reduction of gene expression and the advanced Duke’s stages (Stage C and D).

DLC-1 promoter methylation and KRAS mutations are common concurrent pathological alternations.

Conclusions.

Epigenetic alternation plays a key role in the transcriptional silencing of DLC-1.

It is also an independent risk factor related to the carcinogenesis of colorectal tumors and spans over its pathogenesis process.

Therefore, DLC-1 promoter methylation quantitation may have a promising significance in the evaluation and management of CRC patients.