Takahashi T, Nagai N, Oda H, Ohama K, Kamada N, Miyagawa K
Department of Molecular Pathology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Genes Chromosomes Cancer. 2001 Feb;30(2):196-201. doi: 10.1002/1098-2264(2000)9999:9999<::aid-gcc1078>3.0.co;2-8.
Chromosome rearrangements involving 12q15 are frequently observed in a variety of human mesenchymal tumors. The high mobility group protein gene HMGIC has been identified as the target involved in these rearrangements. Uterine leiomyomas frequently use chromosome band 14q24 as a translocation partner to HMGIC. Recent studies within the chromosome 14 breakpoint region in cell lines carrying t(12;14)(q15;q23-24) revealed that RAD51L1, a member of the RAD51 recombination gene family, is the HMGIC partner. Using RT-PCR, we screened a panel of 81 uterine leiomyomas removed from 30 women for rearrangement between RAD51L1 and HMGIC. This is the first molecular analysis in which primary tumors have been examined for the RAD51L1/HMGIC transcripts. The chimeric transcripts were identified from two cases in which exon 7 of the RAD51L1 gene is fused in frame to either exon 2 or exon 3 of the HMGIC gene. These transcripts encode fusion proteins containing RAD51L1 nucleotide binding domains and the HMGIC protein lacking the N-terminal AT hook motifs. The detection of the RAD51L1/HMGIC fusion in primary tumors adds to the accumulating evidence implicating this fusion in a proportion of uterine leiomyoma patients.
涉及12q15的染色体重排常见于多种人类间充质肿瘤中。高迁移率族蛋白基因HMGIC已被确定为这些重排所涉及的靶点。子宫平滑肌瘤常利用染色体带14q24作为与HMGIC的易位伙伴。最近在携带t(12;14)(q15;q23 - 24)的细胞系中对14号染色体断点区域的研究表明，RAD51重组基因家族成员RAD51L1是HMGIC的伙伴。我们采用逆转录聚合酶链反应（RT-PCR），对从30名女性身上切除的81个子宫平滑肌瘤进行了筛选，以检测RAD51L1和HMGIC之间的重排情况。这是首次对原发性肿瘤进行RAD51L1/HMGIC转录本分子分析。在两例病例中鉴定出嵌合转录本，其中RAD51L1基因的外显子7与HMGIC基因的外显子2或外显子3框内融合。这些转录本编码的融合蛋白包含RAD51L1核苷酸结合结构域以及缺少N端AT钩基序的HMGIC蛋白。在原发性肿瘤中检测到RAD51L1/HMGIC融合，进一步积累了证据，表明这种融合在一部分子宫平滑肌瘤患者中具有重要意义。
