Our main purpose was to identify tumor suppressor gene loci on chromosome 13 responsible for nasopharyngeal cancer (NPC) development by analyzing loss of heterozygosity (LOH) and RB protein expression in paraffin embedded tissues. Normal and tumor DNA were extracted from microdissected samples, and
Three distinct regions of allelic loss at 13q14, 13q21-22, and 13q33 in prostate cancer
β Scribed by Eija-Riitta Hyytinen; Henry F. Frierson Jr.; James C. Boyd; Leland W.K. Chung; Jin-Tang Dong
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 154 KB
- Volume
- 25
- Category
- Article
- ISSN
- 1045-2257
No coin nor oath required. For personal study only.
β¦ Synopsis
Chromosome 13 is one of the most frequently altered chromosomes in cancer, including carcinoma of the prostate. Two known tumor suppressor genes, RB1 and BRCA2, map to chromosome 13; however, recent reports suggest that unknown genes on 13q are more likely to be involved in the development of prostate cancer. In order more fully to define the genetic changes on chromosome 13 in prostate neoplasms, we analyzed 27 polymorphic microsatellite markers spanning the q arm for loss of heterozygosity in 40 primary tumors and in metastases from 11 other patients who died of prostate cancer. Of the 40 primary tumors, 23 (58%) showed LOH for at least one marker. Three distinct regions at q14, q21-22, and q33, defined by markers D13S267 = D13S153, D13S166 = D13S1225, and D13S259 = D13S274, showed the most frequent LOH, suggesting their involvement in the development of prostate cancer. For the 12 patients whose tumors showed LOH at these markers, the average age at diagnosis was 58 years, which was younger than that (63 years, P Ο½ 0.05) for the 28 patients whose tumors lacked LOH. Ten of the 11 (91%) metastases showed LOH with one or more markers. Two of the three most frequently deleted regions (i.e., q14 and q21-22) in the primary tumors and markers linked to the RB1, BRCA2, and EDNRB genes showed high frequencies (56-71%) of LOH in metastases. These results demonstrate that allelic loss on chromosome 13 at q14, q21-22, and q33 occurs in a subset of primary prostate tumors and is a frequent event in metastatic lesions of prostate cancer.
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BACKGROUND. Three regions of chromosome 13 were previously identified for having loss of heterozygosity (LOH) in human prostate cancer. One of them, at 13q33, was defined by LOH at markers D13S158 and D13S280. The XPG/ERCC5 gene, a DNA repair gene that when mutated in the germline leads to xeroderma