Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3.

摘要: Allelic loss at the short arm of chromosome 3 is one most common and earliest events in pathogenesis lung cancer, observed more than 90% small-cell cancers (SCLCs) 50-80% non-small-cell (NSCLCs). Frequent early heterozygosity presence homozygous deletions suggested a critical role region 3p21.3 tumorigenesis deletion was narrowed to 120 kb (ref. 5). Several putative tumour-suppressor genes located 3p21 have been characterized, but none these appear be altered cancer. Here we describe cloning characterization human RAS effector homologue (RASSF1) 120-kb minimal deletion. We identified three transcripts, A, B C, derived from alternative splicing promoter usage. The major transcripts A C were expressed all normal tissues. Transcript missing SCLC cell lines analysed several other cancer lines. Loss expression correlated with methylation CpG-island sequence RASSF1A. highly methylated 24 60 (40%) primary tumours, 4 41 tumours carried missense mutations. Re-expression transcript carcinoma cells reduced colony formation, suppressed anchorage-independent growth inhibited tumour formation nude mice. These characteristics indicate potential for RASSF1A as suppressor gene.