Fusion of the HMGA2 and BNC2 Genes 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) found in several benign tumors appears to be heterogeneous fusing HMGA2 with either BNC2, C9orf92 or NFIB which all three map close to one another within a 3 Mbp region in 9p22. Because the fusion point in HMGA2 in the present tumor lays downstream from the first Let-7 miRNA consensus binding site, we conclude that deletion of the first Let-7 miRNA binding site is not important for the transcriptional upregulation of HMGA2 caused by the genomic rearrangement.

SUBMITTER: Panagopoulos I 

PROVIDER: S-EPMC9677776 | biostudies-literature | 2022 Nov-Dec

REPOSITORIES: biostudies-literature