Vol 49, No 1 (2011)
Original paper
Published online: 2011-04-19
Concomitant hypermethylation of multiple genes in non-small cell lung cancer (NSCLC)
DOI: 10.5603/FHC.2011.0019
Folia Histochem Cytobiol 2011;49(1):132-141.
Abstract
Primary lung cancer remains the leading cause of cancer death worldwide. Promoter hypermethylation
is a major inactivation mechanism of tumor-related genes, and increasingly appears to play an important
role in carcinogenesis. In the present study, we used quantitative methylation-specific PCR (Q-MSP) assays to
analyze promoter hypermethylation of nine genes in a large cohort of well-characterized non-small cell lung
cancer (NSCLC) and explore their associations with the clinicopathological features of tumor. We found that
there were significant differences in methylation levels for six of nine gene promoters between cancerous and
noncancerous lung tissues. More importantly, with 100% diagnostic specificity, high sensitivity, ranging from
44.9% to 84.1%, was found for each of the nine genes. Interestingly, promoter hypermethylation of most genes
was closely associated with histologic type, which was more frequent in squamous cell carcinomas (SCC) than in
adenocarcinomas (ADC). In addition, highly frequent concomitant methylation of multiple genes was found in
NSCLC, particularly in SCC. Our data showed that multiple genes were aberrantly methylated in lung tumorigenesis,
and that they were closely associated with certain clinicopathological features of NSCLC, particularly of
the histologic type, suggesting that these hypermethylated genes could be potential biomarkers in early detection
of NSCLC in high-risk individuals, as well as in evaluating the prognosis of NSCLC patients. (Folia Histochemica
et Cytobiologica 2011, Vol. 49, No. 1, 132–141)
Keywords: DNA methylationmultiple genesquantitative methylation-specific PCR (Q-MSP)non-small cell lung cancer (NSCLC)
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