作者: Montserrat Sanchez-Cespedes , Andre L Reed , Martin Buta , Li Wu , William H Westra
关键词: Cancer research 、 Exon 、 Wild type 、 Biology 、 Tumor suppressor gene 、 Carcinogenesis 、 p14arf 、 Point mutation 、 Squamous carcinoma 、 Retinoblastoma
摘要: Inactivation of the P16 (INK4A)/retinoblastoma (RB) or TP53 biochemical pathway is frequent event in most human cancers. Recent evidence has shown that P14ARF binds to MDM2 leading an increased availability wild type protein. Functional studies also support a putative tumor suppressor gene function for p14ARF suggesting p53 inactivation may be functionally equivalent tumorigenesis. To study relative contribution each tumorigenesis, we analysed and compared alterations p16, genes 38 primary non-small cell lung cancers (NSCLCs) (19 adenocarcinomas 19 squamous carcinoma). The p16 was inactivated 22 (58%) tumors. Twelve these samples (31%) had homozygous deletions by microsatellite analysis; eight them (21%) promoter hypermethylation detected Methylation Specific PCR (MSP) remaining two (5%) harbored point mutation exon 2 sequence analysis. absence protein every case confirmed immunohistochemistry. Fourteen tumors with (12 extending into INK4a/ARF mutations). Mutations were found 18 (47%) nine (50%) inactivation. Thus, inverse correlation not between genetic (P=0.18; Fisher Exact Test). Our data confirm frequently NSCLC. Assuming 9p deletion occurs first, common occurrence suggests abrogation mutation.