A common deletion at chromosomal region 17q21 in sporadic prostate tumors distal to BRCA1

Prostate cancer is the most common cancer in males in the United States, ye t the etiology of this disease is still poorly understood. In previous work from our laboratory, one or more deleted regions were found in prostate tu mors distal to the breast and ovarian cancer susceptibility gene (BRCA1) on chromosome 17. This suggested that genes at 17q21 may play a pivotal role in prostate cancer progression, and there may be new tumor suppressor genes at this locus. We now present a physical map built with P1, P1 artificial chromosome, and bacterial artificial chromosome clones encompassing a DNA s equence anchored by multiple STS markers. The analysis of prostate tumors i ndicated an 85-kb novel commonly deleted interval flanked by D17S1184-D17S1 83-D17S1203-D17S1860, which is at least 470 kb distal to the BRCA1 gene. Fi fty-four of 126 prostrate cancer cases (43%) showed a deletion by a direct FISH technique using P1 probes in this region. Searching with clone end seq uences in the sequence database BLAST, the deleted clone covered genomic DN A sequence that contained upstream binding factor (UBF), EPB3 genes, SHCL1, ASB-4-like sequence, and acidic protein-like sequence. PCR for the ESTs co nfirmed that these genes or ESTs are within the deletion region. Our result s will be helpful for finding candidate tumor suppressor genes in prostate cancer. (C) 2001 Academic Press.