DIFFERENTIAL EXPRESSION AND MUTATION OF THE RAS FAMILY GENES IN HUMANBREAST-CANCER

The expression of ras mRNA levels in 27 human sporadic breast cancer s pecimens was examined, and compared to the corresponding adjacent norm al tissue using the RT-PCR technique. Eighteen out of the 27 specimens (67%) exhibited two- to four-fold increased expression of ras mRNA le vels, compared to corresponding normal tissue. The rates of augmented mRNA expression mere similar among the three ras genes. A statisticall y significant correlation of overexpression of ras genes in specimens classified as Stage I disease was observed, compared to tumors in a mo re advanced stage (II or III). The incidence of codon 12 point mutatio ns of the R-ras gene in fresh tissue samples was also assessed in 61 h uman sporadic breast cancer cases. Point mutations were detected in fo ur (6.5%) out of the 61 cases examined; no correlation was found with any clinicopathological parameter. This is the first report to our kno wledge of the differential expression of the ras family genes in breas t carcinoma. Our findings indicate that the aberrant expression of ras genes may be an initial event in breast cancer oncogenesis and that K -ras point mutations are rarely involved in the development of mammary neoplasias. (C) 1998 Academic Press.