Uterine leiomyomata, or fibroids, are the most common pelvic tumors in females and occur in 20-25% of women of reproductive age. Although benign neoplasms, they constitute a major health problem as 25-50% of affected women experience debilitating symptoms including excessive menstrual bleeding and pelvic discomfort as well as reproductive failure. Fibroids are the major indication for hysterectomy accounting for over 200,000 procedures annually in the United States. Although uterine leiomyomata are three to nine times more frequent in Black than Caucasian women, little is known about this racial predisposition or specific genes involved in their pathogenesis. The major goal of this proposed project is to use contemporary techniques of cytogenetics and molecular biology to identify, isolate and characterize genes involved in the pathogenesis of uterine leiomyomata. A positional cloning approach will be taken by microdissection cloning regions of chromosomes known to be consistently involved in rearrangements in these tumors. Identification and molecular characterization of genes at these sites will contribute to understanding the role of these genes in normal cellular processes and, may facilitate developments in the clinical management of leiomyomata and other solid tumors. Proposed experimental design and methods are: (1) to establish and karyotype cell lines from uterine leiomyoma and matched myometrial specimens, (2) to generate a high density of genomic clones from regions involved in chromosome rearrangements in leiomyomata, (3) to identify genomic clones which span or reside within the chromosomal region of interest, (4) to identify candidate genes within these clones, (5) to assess expression of these genes in normal and neoplastic tissues, and (6) to characterize protein products of the genes.
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