Physical map of 17p13 and the Genes Adjacent to p53

Genetic lesions in the p53 tumor suppressor gene are the most frequently ob served alterations in human cancers. Typically in tumors, one allele of the p53 gene is initially mutated, followed by deletion of the remaining wildt ype allele. In human colon cancer, for example, approximately 70% of late s tage tumors are hemizygous mutant p53. Since the precise gene environment s urrounding the p53 gene is not known, the neighboring genes concomitantly l ost with wildtype p53 deletion remain undetermined. A restriction enzyme ma p and clone array of 1.1 Mb surrounding the p53 gene were constructed using a combination of YAC, BAG, NotI linking, and NotI jumping clones. The resu lting physical map and clone array include approximately 400 kb telomeric a nd 700 kb centromeric to the p53 gene. Sequence determination and analysis adjacent to NotI and AscI sites, indicative of CpG islands, allowed the rap id identification of numerous genes within the cloned region. Twenty-seven transcription units were identified, including 18 characterized genes. Limi ted analysis of primary human colon tumors, hemizygous for the p53 gene, in dicates loss of the entire 1.1-Mb region upon deletion of wildtype p53. (C) 2000 Academic Press.