Microsatellite alterations on chromosome 9 in chewing tobacco-induced oralsquamous cell carcinomas from India

Genomic instability as reflected by microsatellite alterations in specific target regions is an important characteristic of oral squamous cell carcino ma (OSCC). Microsatellite instability (MSI) and loss of heterozygosity (LOH ) on chromosome 9 has been reported as an early event in oral cancers, prim arily from patients in the USA and UK. Hence. we examined 77 primary oral c ancer tissues and corresponding peripheral blood cell (PBC) DNR from Indian oral cancer patients for LOH and MSI, using a panel of 11 microsatellite m arkets spanning chromosome 9 on p and q arms. The patients were long-time ( minimum 10 years) tobacco chewers. The matched DNA samples were amplified b y polymerase chain reaction, resolved on a denaturing polyacrylamide gel an d visualized by silver staining. An overall of 62% (48/77 cases) of the pat ients demonstrated microsatellite alterations including 27% MSI and 52% LOH . although at individual loci MSI was observed in 3-8% patients and LOH in the informative cases ranged from 4 to 41%. A majority of the alterations o ccurred on the p arm at 9p21-23, with 85% (41/48 cases) genetic alterations concentrated between markers D9S157 and D9S161. Multiple alterations were seen in 56% (27/48) of the affected cases with 17 patients showing microsat ellite alterations in three to eight loci. Our data show the incidence of g enetic alterations primarily in the chromosomal region 9p21-73, and may be indicative of involvement of p16 (CDKN2) tumor suppressor gene on chromosom e 9p21, in a subset of chewing tobacco-induced oral cancers. (C) 2000 Elsev ier Science Ltd. All rights reserved.