NOEY2 (ARHI), an imprinted putative tumor suppressor gene in ovarian and breast carcinomas

Using differential display PCR, we have identified a gene [NOEY2, ARHI (des ignation by the Human Gene Nomenclature Committee)] with high homology to r as and rap that is expressed consistently in normal ovarian and breast epit helial cells but not in ovarian and breast cancers. Reexpression of NOEY2 t hrough transfection suppresses clonogenic growth of breast and ovarian canc er cells. Growth suppression was associated with down-regulation of the cyc lin DI promoter activity and induction of p21(WAF1/CIP1). In an effort to i dentify mechanisms leading to NOEY2 silencing in cancer, we found that the gene is expressed monoallelically and is imprinted maternally. Loss of hete rozygosity of the gene was detected in 41% of ovarian and breast cancers. I n most of cancer samples with loss of heterozygosity, the non-imprinted fun ctional allele was deleted. Thus, NOEY2 appears to be a putative imprinted tumor suppressor gene whose function is abrogated in ovarian and breast can cers.