5 ' CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer

Allele loss and loss of expression of fragile histidine triad (FHIT), a put ative tumor suppressor gene located in chromosome region 3p14.2, are freque nt In several types of cancers. Tumor-acquired methylation of promoter regi on CpG islands is one method for silencing tumor suppressor genes, We inves tigated 5' CPG island methylation of the FHIT gene in 107 primary non-small cell lung cancer (NSCLC) samples and corresponding nonmalignant lung tissu es, 39 primary breast carcinomas, as well as in 49 lung and 22 breast cance r cell lines by a methylation-specific PCR assay. In addition, we analyzed brushes from the bronchial epithelium of 35 heavy smokers without cancer, F HIT methylation was detected in 37% of primary NSCLCs, 31% of primary breas t cancers, and 65% of lung and 86% of breast cancer cell lines. The Frequen cy of methylation in small cell and NSCLC cell lines were identical. Methyl ation was found in 9% of the corresponding nonmalignant lung tissues and in 17% of bronchial brushes from heavy cigarette smokers. FHIT methylation wa s significantly correlated with loss of FHIT mRNA expression by Northern bl ot analysis in lung ranter cell lines and with loss of Fhit expression in N SCLC and breast tumors by immunostaining. We conclude that methylation of F HIT is a frequent event in NSCLC and breast cancers and is an important mec hanism for loss of expression of this gene. Methylation of FHIT commences d uring lung cancer pathogenesis and may represent a marker for risk assessme nt.