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Whole Genome Amplification and High-Throughput Allelotyping Identified Five Distinct Deletion Regions on Chromosomes 5 and 6 in Microdissected Early-Stage Ovarian Tumors¹

Laboratory of Gynecologic Oncology, Division of Gynecologic Oncology, and Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Dana Farber Harvard Cancer Center; Harvard Medical School, Boston, Massachusetts 02115 [V. W. W., S. C. M., R. S. B.], and Department of Pathology, Massachusetts General Hospital, Dana Farber Harvard Cancer Center; Harvard Medical School, Boston, Massachusetts 02114 [D. A. B.]

Investigation of genetic changes in tumors by loss of heterozygosity is a powerful technique for identifying chromosomal regions that may contain tumor suppressor genes. In this study, we determined allelic loss on chromosomes 5 and 6 in 29 primary early-stage epithelial ovarian carcinomas including 3 microscopically identified adenocarcinomas using a high-throughput PCR-based method combined with laser capture microdissection and whole genome amplification techniques. Twenty microsatellite markers spanning chromosomes 5 and 6 at an average distance of 20 cM were examined. High frequencies of loss on chromosome 5 were identified at loci D5S428 (48%), D5S424 (32%), and D5S630 (32%). Our study also showed that chromosome 6 exhibited high frequencies of loss of heterozygosity at loci D6S1574 (46%), D6S287 (42%), D6S441 (45%), D6S264 (60%), and D6S281 (35%). These results suggest that multiple tumor suppressor genes are located on five distinct regions on chromosomes 5 and 6, i.e., 5p15.2, 5q13–21, 6p24–25, 6q21–23, and 6q25.1–27, and may be involved in the early development of ovarian carcinomas.

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