Short communicationshREC2, a RAD51-like Gene, is Disrupted by t(12;14)(q15;q24.1) in a Uterine Leiomyoma
Introduction
Leiomyoma is a benign tumor of smooth muscle which occurs most frequently in the uterus and is diagnosed in 20 to 50% of women of reproductive age [1]. Approximately 20% of uterine leiomyomas (ULs) show a recurrent chromosomal translocation, t(12;14)(q15;q24.1) which is often the sole detectable cytogenetic aberration [2], suggesting that it may represent an early event in the pathogenesis of leiomyoma. The consistent involvement of specific regions of chromosomes 12 and 14 in karyotypic changes in leiomyoma and related tumors has led to considerable speculation on the presence of genes with tumorigenic potential in these genomic regions 3, 4. Other investigators have previously reported the cloning of a 450 kb multiple aberration region (MAR) on chromosome 12 within which several t(12;14) breakpoints have been shown to map, and implicated the high mobility group protein C (HMGI-C) gene in leiomyoma and other tumors of mesenchymal origin 5, 6.
Relatively little is known about the region of chromosome 14 involved in t(12;14). We previously reported the isolation of DNA clones spanning the breakpoints on chromosome 14 of three uterine leiomyomas [7], and the identification of several expressed sequences that mapped within these clones [8]. One of these expressed sequences, hREC2 [9], is a putative member of the RAD51/52 family of double strand break repair enzymes, which play a key role in DNA recombination. A 1.8 kb hREC2 cDNA sequence (Genbank accession #U92074) has been shown to be expressed in all tissues tested, although the detection of transcripts of other sizes suggested that there are alternative splice forms [9]. We have previously shown that hREC2 is localized within the leiomyoma breakpoint cluster region (BCR) on chromosome 14 [8]. Here, we show that the genomic structure of hREC2 is interrupted by t(12;14)(q15;q24.1) in a UL. This translocation results in the loss of a 656 base pair (bp) exon that contains five carboxyl-terminal codons and the entire 3′ UTR of the ubiquitously expressed hREC2 isoform.
Section snippets
Materials and methods
Physical mapping of 14q24.1 was used to identify DNA clones that spanned translocation breakpoints from ULs 7, 8. Sequences of putative exons isolated by exon amplification [10] from two of these clones, bacterial artificial chromosome (BAC) 52F18 and cosmid 90C5, were used for homology searches of the expressed sequence tag database (dbEST) using the basic local alignment search tool (BLAST) [11]. These analyses resulted in the identification of an EST clone (GenBank Accession #T92120) that
Results
Physical mapping and exon trapping from 14q24.1 resulted in the identification of sequences corresponding to hREC2. This gene was first described by Rice and coworkers [9] as a human homolog of the Ustilago maydis recombinational repair gene REC2, and a nearly identical cDNA sequence (hRAD51B) was reported by Albala et al. [13]. Cartwright and coworkers [14] subsequently reported the identification of a novel gene, R51H2 (Genbank Accession #Y15571), with DNA sequence identical to the hREC2 cDNA
Discussion
Double-strand DNA breaks (DSBs) occur in a number of natural cellular processes including DNA replication, meiotic recombination, and immunoglobulin gene rearrangement. DSBs are also induced by genotoxic agents such as biradicals, high energy radiation, and reactive oxygen species (reviewed in [17]). Therefore, the DSB repair enzymes, which include RecA in prokaryotes (reviewed in [18]) and the RAD51/52 gene family in eukaryotes (reviewed in [19]), play a critical role in the maintenance of
Acknowledgements
The authors thank T. Smolarek and C. Krane for critical reading of the manuscript. Support for this work was provided in part by grant RO1-CA67315 to A.G.M. from the National Institutes of Health and a grant to S.K. from the Department of Radiology, University of Cincinnati.
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