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THE BALANCED, RECIPROCAL TRANSLOCATION OF CHROMOSOMAL SUBBANDS 12q15 AND 14q24 AND ALTERED GENE EXPRESSION IN UTERINE LEIOMYOMA

INGRAHAM, SUSAN ELIZABETH

Abstract Details

2002, PhD, University of Cincinnati, Medicine : Molecular Genetics, Biochemistry and Microbiology.
A balanced, reciprocal translocation between chromosomes 12 and 14 is frequently observed in uterine leiomyoma (UL), a common benign smooth muscle tumor. Cytogenetic evidence suggests that t(12;14)(q15;q24) is an early event and therefore may represent one of the important steps in UL pathogenesis. The breakpoints of t(12;14)(q15;q24) have been localized to unusually large genomic regions (approximately 0.5 Mb) on each of the involved chromosomes. In this study, we investigated the molecular events associated with this translocation, specifically the transcription of genes within the breakpoint regions on 14q24 and 12q15. t(12;14)(q15;q24) had previously been associated with activation of HMGA2 on chromosome 12, a gene implicated in promoting cell proliferation, particularly of lipoid tissues. We analyzed this gene and discovered several novel transcripts from 12q15 that are embedded within HMGA2 . On chromosome 14, the breakpoint in one UL was found to lie within RAD51L1 , a putative DNA repair and recombination gene. Subsequent analysis of two additional t(12;14) UL breakpoints refined the chromosome 14 breakpoint region to between 700 and 1200 kb.The large size of the breakpoint regions and the mapping of breakpoints well outside both HMGA2 and RAD51L1 suggested that the translocation may alter the structure and long-range regulatory controls of genes including but perhaps not limited to HMGA2 and RAD51L1 . To test this hypothesis, an expression map was developed which consisted of ESTs and genes within and flanking both breakpoint regions. Expression of these markers was tested in matched normal and t(12;14) ULtissue samples to identify a domain of altered expression on chromosomes 12 and 14. HMGA2 and the three novel ESTs embedded within HMGA2 ., A15, B6, and D12, were overexpressed six- to more than twenty-fold, while RAD51L1 and other ESTs on chromosome 14 were not consistently or significantly altered in UL. Positional cloning of the UL breakpoint region and mapping of the domain of altered expression in tumors sets the stage for understanding the molecular mechanism for the pathogenesis of UL.
Dr. Anil G. Menon (Advisor)
182 p.

Recommended Citations

Citations

  • INGRAHAM, S. E. (2002). THE BALANCED, RECIPROCAL TRANSLOCATION OF CHROMOSOMAL SUBBANDS 12q15 AND 14q24 AND ALTERED GENE EXPRESSION IN UTERINE LEIOMYOMA [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1029433658

    APA Style (7th edition)

  • INGRAHAM, SUSAN. THE BALANCED, RECIPROCAL TRANSLOCATION OF CHROMOSOMAL SUBBANDS 12q15 AND 14q24 AND ALTERED GENE EXPRESSION IN UTERINE LEIOMYOMA. 2002. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1029433658.

    MLA Style (8th edition)

  • INGRAHAM, SUSAN. "THE BALANCED, RECIPROCAL TRANSLOCATION OF CHROMOSOMAL SUBBANDS 12q15 AND 14q24 AND ALTERED GENE EXPRESSION IN UTERINE LEIOMYOMA." Doctoral dissertation, University of Cincinnati, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1029433658

    Chicago Manual of Style (17th edition)