ANALYSIS OF HPV-POSITIVE AND HPV-NEGATIVE VULVAR CARCINOMAS FOR ALTERATIONS IN C-MYC, HA-RAS, KI-RAS, AND N-RAS GENES

Mutation or overexpression of certain host genes, including c-myc, Ha- ras, and Ki-ras, have been associated with genital squamous neoplasia, specifically in the cervix, and have been implicated in the natural h istory of these tumors. The relationship of these host gene alteration s to vulvar squamous cell carcinomas has not been previously studied. We analyzed archival material from 13 human papillomavirus-positive an d-negative vulvar squamous cell carcinomas for mutations in Ha-, Ki-, and N-ras genes, and a smaller number of fresh samples for c-myc ampli fication, using PCR-based assays. For comparison, eight cervical squam ous cell carcinomas (three fixed and five fresh) were also analyzed. A nalysis for ras mutations revealed a previously reported silent alleli c variant at nucleotide 1744 in the Ha-ras gene, but no mutations in c odons 12, 13, or 61. Similarly, genomic amplification of c-myc beyond a maximum of three haploid copies was not identified in the cases. The se findings indicate that alterations in myc or ras sequences are not linked to vulvar squamous cell carcinomas or to the presence or absenc e of HPV nucleic acids. Moreover, they apparently will not distinguish vulvar from cervical carcinomas, both groups appearing to be unlikely to harbor these sequence alterations. (C) 1994 Academic Press, Inc.