Novel gene fusion ofCOX6C at 8q22-23 toHMGIC at 12q15 in a uterine leiomyoma

Abstract

Cytogenetic analyses have shown that aberrations involving 12q13–15 are frequent chromosomal changes in a variety of human benign mesenchymal tumors, e.g., pleomorphic adenomas of the parotid gland, pulmonary chondroid hamartomas, lipomas, and uterine leiomyomas. Recently, the high‐mobility group protein gene HMGIC was identified as the target gene affected by the 12q13–15 aberrations. Using 3′ rapid amplification of cDNA ends experiments, we isolated novel ectopic sequences fused to HMGIC in a uterine leiomyoma. Cloning of the fusion cDNA identified the human cytochrome c oxidase subunit VIc (COX6C) gene on 8q22–23 as the fusion partner of HMGIC. Nucleotide sequences of the fusion transcript revealed that the first 3 exons of the HMGIC gene, encoding the 3 DNA binding domains, was fused to the exon 2 of the COX6C gene. The identification of a gene rearrangement suggests a role for HMGIC in tumorigenesis of uterine leiomyoma and suggests a possible involvement of HMGIC in mesenchymal differentiation. Genes Chromosomes Cancer 27:303–307, 2000. © 2000 Wiley‐Liss, Inc.

Fusion of a Sequence from HEI10 (14q11) to the HMGIC Gene at 12ql5 in a Uterine Leiomyoma

“…[16][17][18][19][20] We recently suggested that the contribution of partner genes to the pathogenesis of uterine leiomyomas was likely to be limited because the C-terminal part derived from one partner gene, COX6C, encoded only a few amino acids. 8) The results of the present study are consistent with that proposition.…”

“…Until now, only a few genes, e.g. ALDH2, 6) RAD51B, 7) and COX6C 8) were known to be fused with HMGIC in uterine leiomyomas, but we suspected that other genes might also have this property. Using 3′ rapid amplification of cDNA ends (3′RACE) and reverse transcriptase-polymerase chain reactions (RT-PCRs), we screened 16 uterine leiomyomas and identified a novel fusion partner of HMGIC in one of those tumors.…”

Evidence forRAD51L1/HMGIC fusion in the pathogenesis of uterine leiomyoma

“…These findings suggest that the mechanism of HMGIC dysfunction in uterine leiomyoma is different from that in lipoma. It is noteworthy, however, that the HMGIC AT hook motifs are fused to ectopic sequences including exon 13 of the mitochondrial aldehyde dehydrogenase gene (Kazmierczak et al, 1995) and exon 2 of the cytochrome c oxidase subunit VIc gene (Kurose et al, 2000) in a minority of uterine leiomyoma.…”

Detection and screening of chromosomal rearrangements in uterine leiomyomas by long‐distance inverse PCR

“…Chromosomal rearrangements involving HMGA2 are clustered 10 to 100 kb upstream of the 5′ untranslated region of HMGA2 (Schoenberg Fejzo et al, ; Schoenmakers et al, ; Quade et al, ). Rearrangements involving the intragenic region of HMGA2 have also been reported (Kazmierczak et al, ; Kurose et al, ; Mine et al, ; Velagaleti et al, ). On the other hand, within RAD51B , one of the most frequent fusion partners of HMGA2 , breakpoints cluster between exons 5 and 11 (Schoenmakers et al, ; Takahashi et al, ; Quade et al, ).…”