Loss of expression and aberrant methylation of the CDH13 (H-cadherin) genein breast and lung carcinomas

Expression of some members of the cadherin family is reduced in several hum an tumors, and CDH13 (B-cadherin), located on chromosome 16q24.2-3, may fun ction as a tumor suppressor gene. In human tumors, loss of expression of ma ny tumor suppressor genes occurs by aberrant promoter region methylation. W e examined the methylation status of the CDH13 promoter in breast and lung cancers and correlated it with mRNA expression using methylation-specific P CR and reverse transcription-PCR Methylation was frequent in primary breast tumors (18 of 55, 33%) and cell lines (7 of 20, 35%). In lung cancers, met hylation was present more frequently in non-small cell lung cancer tumors ( 18 of 42, 43%) and cell lines (15 of 30, 50%) than in small cell Lung cance r cell Lines (6 of 30, 20%; P = 0.03). Only the methylated or unmethylated forms of the gene were present in most (73 of 80, 91%) tumor cell lines. CD H13 expression was present in 24 of 30 (80%) of nonmethylated tumor lines, All 18 methylated lines tested lacked expression irrespective of whether th e unmethylated form was present, confirming biallelic inactivation in methy lated lines, Gene expression was restored in all five methylated cell lines tested after treatment with the demethylating agent 5 ' -aza-2-deoxycytidi ne. Our results demonstrate frequent aberrant methylation of CDH13 in breas t and lung cancers accompanied by loss of gene expression, although express ion may occasionally be lost by other mechanisms.