The human c-Ha-nzs2 is a processed pseudogene inactivated by numerous base substitutions

The human c-Ha-ras2 gene, one of two known members of the Harvey ras family, ia reportedly located on the X-chromosome and has lost introns (1, 2). There has heretofore been no information on its precise gene structure and oncogenic potential. He have determined the nucleotide sequence of the c-Ha-ras2 and demonstrate that it is a processed pseudogene surrounded by several direct repeats and contains numerous base substitutions as well as a notable mutation (AGT at codon 12 of the p21 protein) responsible for oncogenic conversion of the knovn ras genes (3-8). rUTRODPCTION Normal human DNA contains sequences related to retroviral oncogenes, and activation of these proto-oncogenes is considered to be involved in ex-pression of the transformed phenotype in naturally occurring tumors. The transfection assay of NIH 3T3 cells with tumor DNA disclosed activated ver-sions of ras-related proto-oncogenes (9-16), comprised of at least three members (c-Ea-rag, c-Ki-ras and N-ras) (17), in human solid tumors, cell lines of epithelial origin and certain types of hematopoietic malignancies (18, 19). Based on hybridization analysis, the human genome was found to contain additional cellular homologues of transforming genes of the Harvey and Kirsten murine sarcoma viruses (1). As characterization of normal ras-related sequences and determination of their exact numbers might be of clinical significance in the diagnosis and prevention of cancer, we attempted to identify homologous sequences by screening a human genomic DNA library using the v-Ha-ras probe at various hybridization stringency. Among these clones, we report here the nucleotide sequence of the c-Ha-ras2 and demonstrated that it is a processed and inactivated pseudogene accompanied by several direct repeats