THE COMMONLY DELETED REGION AT 9P21-22 IN LYMPHOBLASTIC LEUKEMIAS SPANS AT LEAST 400 KB AND INCLUDES P16 BUT NOT P15 OR THE IFN GENE-CLUSTER

Chromosome band 9p21-22 is one of the most common targets for deletion s in cancer. The pie tumor suppressor gene maps to this region and is inactivated in a wide variety of tumor cell lines and primary tumors. However, in some of the neoplasms with frequent 9p21 loss of heterozyg osity (LOH), a structurally and functionally normal pie is found sugge sting that this gene might not be the primary or only target for inact ivation. To define the smallest region of overlap of deletions at chro mosome band 9p21-22 and to clarify the involvement of p16, p15 and the IFN cluster gene in lymphoblastic leukemias, we used a multiplex poly merase chain reaction to construct a detailed map of deletions at 9p21 -22. We studied DNA from 30 lymphoblastic leukemia patients and nine c ell lines using 10 genes/markers that map to this region, including fo ur STS markers located between pie and D9S171 (STS1, STS2) or between pie and IFN alpha (STS3, STS4). We found that the size of the deletion s in this region is variable and that the commonly deleted region span s at least 400 kb; it includes the p16 gene but excludes the IFN gene cluster and the p15 gene. The identification of this commonly deleted region enables a more focused search for other putative tumor suppress or gene at 9p21 which could be relevant to leukemogenesis.