Deletion of two regions on chromosome 4 in bladder carcinoma: definition of a critical 750kB region at 4p16.3.

Loss of heterozygosity (LOH) of chromosome 4 has been identified in several human tumours including carcinomas of colorectum, ovary, liver and head and neck. LOH at loci on chromosome 4p has previously been identified in 22% of primary bladder tumours. We have assessed LOH in 178 bladder tumours using a panel of six microsatellite markers. Thirty-four tumours (19%) showed LOH at one or more loci. Twenty-three deletions involved restricted regions of 4p and could be used to define two common regions of deletion. A very small common region between D4S43 and D4S127 (estimated to be approximately 750 kB) was involved in 14/23 (61%) of 4p deletions. A second common region centromeric to D4S174 was deleted in 7/23 (30%) of tumours with deletions. Two tumours (9%) had deletions involving both regions independently. Previous functional studies have demonstrated both a senescence function and a suppressor of tumorigenicity on human chromosome 4. Localisation of the common regions of deletion in bladder tumours provides a starting point for positional cloning of the gene(s) concerned and for more precise comparative functional studies.