Mapping of the shortest region of overlap of deletions of the short arm of chromosome 9 associated with human neoplasia

Abstract

Deletions of the short arm of chromosome 9 with a minimum region of overlap at band 9p22 are frequently observed in acute lymphoblastic leukemia and in gliomas. They also occur at a lower frequency in lymphomas, melanomas, lung cancers, and other solid tumors. These deletions often include the entire interferon (IFN) gene cluster, which comprises about 26 interferon-alpha (IFNA), -omega (IFNW), and-beta-1 (IFNB1) interferon genes, as well as the gene for the enzyme methylthioadenosine phosphorylase (MTAP). By comparing microscopic deletions with the genes lost at the molecular level, we have determined the order of these genes on 9p to be telomere-IFNB1-IFNA/IFNW cluster-MTAP-centromere. In a few cell lines and in primary leukemia cells, we have observed deletions that have breakpoints within the IFN gene cluster and result in partial loss of the IFN genes. These partial deletions allowed us to determine the order of some genes or groups of genes within the IFNA/IFNW gene cluster. Our current results map the shortest region of overlap of these deletions in the various tumors to the region between the centromeric end of the IFNA/IFNW gene cluster and the MTAP gene locus.