Cytogenetic and molecular analysis of chromosomal translocations in uterine leiomyoma.

摘要

Many genes involved in human malignancy have been identified, leading to a better understanding of the etiology of different cancers. Like malignant tumors, benign tumors may also have a genetic basis, but until recently there has been little emphasis on identification and study of "benign" genes. The goal of this thesis was to identify gene(s) involved in the initiation and/or progression of uterine leiomyomata and other benign tumors of mesenchymal origin. Our cytogenetic studies of these tumors provided evidence that a gene on chromosome 12 in bands q14-q15 may be involved in the etiology of benign mesenchymal neoplasia. We used a positional cloning strategy to identify a YAC spanning the chromosome 12q14-q15 translocation breakpoint, one of the most consistently rearranged regions identified in benign neoplasms. Ultimately, we mapped the translocation breakpoints in uterine leiomyomata, pulmonary chondroid hamartoma, and lipoma and provided evidence that a candidate gene, HMGI-C, may be involved in the pathobiology of these tumors. Understanding the role HMGI-C plays in benign mesenchymal neoplasia may elucidate critical differences between benignancy and malignancy. In addition, although benign tumors such as uterine leiomyomata are not life-threatening, they are a significant health problem, and a better understanding of the genetics of these tumors may lead to more effective medical treatments.