[DNA methylation of tumor suppressor genes located on chromosome 3p in non-small cell lung cancer]

[非小细胞肺癌中位于3p染色体上的抑癌基因的DNA甲基化]

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Abstract

BACKGROUND AND OBJECTIVE: DNA methylation is one of the mechanisms of epigenetics. Allelic loss located on chromosome 3p happen frequently and early in non-small cell lung cancer (NSCLC). The aim of this study is to detect the promoter methylation status of tumor suppressor genes (TSGs) located on chromosome 3p in NSCLC and to evaluate its correlation with clinicopathological features. METHODS: A total of 78 paired NSCLC specimens and their adjacent normal tissues were collected in the study. Promoter methylation status was determined by methylation-specific polymerase chain reaction (MSP). DLEC1 gene expression was determined by RT-PCR and immunohistochemistry. RESULTS: Aberrant methylation frequency of DLEC1, RASSF1A, hMLH1, RARβ and FHIT genes detected in 78 NSCLC tissues were 41.03%, 39.74%, 30.77% and 16.67%, respectively, which were all significantly higher than that in adjacent normal tissues. However, FHIT gene was not detected methylation in both cancerous and non-cancerous tissues. DLEC1 hypermethylation was associated with advanced stage (P=0.011) and lymph metastasis (P=0.019), while RASSF1A, RARβ, hMLH1 and mean methylation index (MI) were not correlated with any clinicopathological parameters. Moreover, DLEC1 gene downregulation was detected in 56.41% (44/78) NSCLC tissues and correlated with promoter hypermethylation. CONCLUSIONS: Frequent hypermethylation of TSGs located on chromosome 3p was a common event contributing to NSCLC pathogenesis and DLEC1 methylation was closely correlated with loss of expression.

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