title: Loss of heterozygosity for chromosomal regions 15q14-21.1, 17q21.31, and 13q12.3-13.1 and its relevance for prostate cancer.
abstract: Although prostate cancer is one of the most common cancers in men, the genetic defects underlying its pathogenesis remain poorly understood. DNA damage repair mechanisms have been implicated in human cancer. Accumulating evidence indicates that the fidelity of the response to DNA double-strand breaks is critical for maintaining genome integrity. RAD51 is a central player in double-strand break repair via homologous recombination, and its alterations may confer and increase the risk of cancer. RAD51 functioning depends on the indirect or direct interactions with BRCA1 and BRCA2. To evaluate the contribution of RAD51 to sporadic prostate cancer, loss of heterozygosity (LOH) for chromosomal region 15q14-21.1 (RAD51 locus) was determined and compared to LOH in 17q21.31 (BRCA1 locus) and 13q12.3-13.1 (BRCA2 region). DNA was isolated from prostate biopsies and matched peripheral blood of 50 patients. The regions 15q14-21.1, 17q21.31, and 13q12.3-13.1 were examined using microsatellite markers on chromosome 15 (D15S118, D15S214, D15S1006), chromosome 17 (D17S855, D17S1323), and chromosome 13 (D13S260, D13S290), respectively. The LOH in tumors was analyzed by PCR with fluorescently labeled primers and an ABI PRISM 377 DNA Sequencer. Allele sizing was determined by GeneScan version 3.1.2 and Genotyper version 2.5 software (Applied Biosystems, USA). LOH was identified in 57.5, 23, and 40 % for chromosomal regions 15q14-21.1, 17q21.31, and 13q12.3-13.1, respectively. Twenty-six percent of studied cases manifested LOH for at least one marker in 15q14-21.1 exclusively. A significant correlation was found between LOH for studied region and PSAD (prostate-specific antigen density). The findings suggest that RAD51 may be considered as a prostate cancer susceptibility gene.
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236, Lodz, Poland. mnz@biol.uni.lodz.pl.
authors.forename: Maria
authors.initials: M
authors.lastname: Nowacka-Zawisza
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236, Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Forma
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236, Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Walczak
authors.affiliation: 2nd Department of Urology, Medical University of Lodz, Pabianicka 62, 93-513, Lodz, Poland.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Różański
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bryś
authors.affiliation: Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236, Lodz, Poland.
authors.forename: Wanda M
authors.initials: WM
authors.lastname: Krajewska
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D051135:Rad51 Recombinase / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C495153:RAD51 protein, human; D051135:Rad51 Recombinase
keywords: Loss of heterozygosity (LOH); Molecular markers; Prostate cancer; RAD51