Fusion of theHMGA2andBNC2Genes in Uterine Leiomyoma With t(9;12)(p22;q14)

Abstract

Background/Aim: The translocation t(9;12) (p22;q14~15) has been reported in lipomas, pleomorphic adenomas, a myolipoma, two chondroid hamartomas, and two uterine leiomyomas. In lipomas and pleomorphic adenomas, the translocation fuses HMGA2 (12q14) with the NFIB gene from 9p22; in myolipoma, it fuses HMGA2 with C9orf92 from 9p22; and in chondroid hamartomas, fluorescence in situ hybridization (FISH) investigations showed the chromosomal aberration to cause intragenic rearrangement of HMGA2. The translocation's molecular consequence in a uterine leiomyoma is described here. Materials and Methods: A typical leiomyoma was investigated using banding cytogenetics, FISH, RNA sequencing, reverse transcription polymerase chain reaction and Sanger sequencing. Results: A single translocation, t(9;12)(p22;q14) leading to an HMGA2::BNC2 chimera, was found in tumor cells. A sequence of the untranslated part of exon 5 of HMGA2 (nucleotide 1035 in the NCBI reference sequence NM_003483.4) had fused with a sequence from the untranslated part of exon 7 of BNC2 from 9p22 (nucleotide 9284 in reference sequence NM_017637.6). Conclusion: At the molecular level, the t(9;12)(p22;q14~15

Fusion of the High-mobility Group AT-Hook 2 (HMGA2) and the Gelsolin (GSN) Genes in Lipomas With t(9;12)(q33;q14) Chromosomal Translocation

“…An in-frame fusion transcript of HMGA2 with the Yes1-associated transcriptional regulator gene (YAP1) from 11q22 was reported in an aggressive angiomyxoma (54). Recently, fusion of HMGA2 with the nuclear receptor co-repressor 2 gene (NCOR2) from 12q24.31 was described; the result is an HMGA2::NCOR2 chimeric protein found in osteoclastic giant cell-rich tumors of bone (31), giant cell-rich soft-tissue tumors expressing low-to high molecular weight keratins (55), in vivo 37: 524-530 (2023) xanthogranulomatous epithelial tumor (56), and tenosynovial giant-cell tumor (57). Tumorigenic properties were detected for both the HMGA2::LPP (58-60) and HMGA2::EGFR fusion proteins (53), whereas functional studies have not been performed to test for the effects of HMGA2::YAP1, HMGA2::NCOR2, and the present HMGA2::GSN chimeric protein.…”

“…Methods. All methods used in the present study have been described in many of our previous publications (14, [28][29][30][31][32][33][34][35]. In brief, for cytogenetic analysis, samples from the surgical specimens were disaggregated and the resulting cells were cultured, harvested, and processed for cytogenetic examination using standard techniques (36,37).…”