The RecQ family of DNA helicases is highly conserved in evolution from bacteria to mammals. There are five human RecQ family members, RECQ1, BLM (RECQ2), WRN (RECQ3), RECQL4 and RECQ5. A defect in the RecQ family helicase encoded by the BLM and WRN genes gives rise to Bloom and Werner syndrome. The mutations of RECQL4 have been associated with at least a subset of cases of both Rothmund-Thomson syndrome and RAPADILINO. The most characteristic features of these diseases are predisposition to the development of malignancies of different types, some aspects of premature aging, and on the cellular level, genome instability.
In this study, we evaluated BLM, WRN and RECQL4 promoter methylation status by methylation-specific PCR analysis in 132 patients with primary lung cancer. The WRN promoter was in non-small cell lung carcinoma (NSCLC) but not in small cell lung carcinoma (SCLC). In normal lung tissues analyzed, the methylation of WRN gene was not detected. The incidence of methylation in tumors was significantly higher in NSCLC than in SCLC (P = 0.013). The methylation of both BLM and RECQL4 promoters was not detected in all the samples tested. In Japanese lung cancer, the methylation of WRN promoter was observed in all histological subtypes of NSCLC, including adenocarcinoma (11 of 44, 25%), squamous cell carcinoma (2 of 38, 5.3 %), and large cell carcinoma (9 of 28, 32 %), through its frequency is significantly lower in SCC than in other two cell types.
Moreover, we analyzed BLM, WRN and RECQL4 promoter methylation status using 39 tumor cell lines, consisting of lung, colon, stomach, breast, ovary, brain, renal, and prostate cancer. The methylation of WRN gene was significantly higher in breast, stomach and colon cancer cell lines. The methylation of both BLM and RECQL4 promoters was not detected in all 39 tumor cell lines tested.
These data demonstrated that the methylation status of WRN gene was different in different tumors or histological subtypes, suggesting its distinct roles in each tumor site or tumor histology.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA