Molecular-cytogenetic refinement of the 12q14-->q15 breakpoint region affected in uterine leiomyomas.

Recent molecular and cytogenetic studies on uterine leiomyoma cell lines with aberrations in 12q14-->q15 have shown that the chromosome 12 breakpoints seem to cluster in a 260-kb region designated as ULCR 12 (uterine leiomyoma cluster region of chromosome 12 breakpoints). Here we report the results of fluorescent in situ hybridization (FISH) studies using a molecular probe composed of five different cosmids that cover a 700-kb region encompassing ULCR 12. The FISH studies were performed on primary tumor specimens of uterine leiomyomas. With the exception of one case, our results demonstrated that the cosmid pool bridges the breakpoint region 12q14-->q15 in primary tumors as well. In the remaining case signal was localized distal to the breakpoint, indicating a breakpoint outside the region covered by the cosmid pool or a deletion in the region surrounding the chromosome 12 breakpoint. Individual cosmid probes from the pool were then used to narrow the localization of the breakpoint region in both the primary leiomyomas and established cell lines. The results showed that the breakpoints involving 12q14-->q15 in the primary uterine leiomyomas and derived cell lines are clustered in a single 170-kb breakpoint region within ULCR 12. For three of the cell lines studied, the breakpoint map within a 40-kb segment covered by one cosmid.