Hypermethylation of the CpG island of the RASSF1A gene in ovarian and renal cell carcinomas.

Abstract

Homozygous deletion and loss of heterozygosity (LOH) at chromosome 3p21 have been observed in several types of human cancer including lung cancer and breast cancer. In previous work, we cloned and identified the human RAS association domain family 1A gene (RASSF1A) from the lung tumor suppressor locus 3p21.3. The CpG island and promoter region of RASSF1A is highly methylated in primary lung and breast tumors. In this study, we analyzed the methylation status of the promoter region of RASSF1A in 3 different tumor types: colon, ovarian and renal cell carcinoma. In colon cancers, 3 out of 26 tumor tissues (12%) were methylated at the CpG island of the RASSF1A gene. Renal and ovarian cancers showed a much higher frequency of methylation. For ovarian tumors, 8 out of 20 tumors (40%) were methylated. In renal cell carcinomas, 18 out of 32 cases (56%) were methylated. For all tumor types, none of the available normal tissues was methylated. This data suggests that methylation of the CpG island and promoter of the RASSF1A gene is common not only in lung and breast tumors but also in renal cell carcinoma and ovarian cancer.