Fusion of the HMGA2 and C9orf92 genes in myolipoma with t(9;12)(p22;q14)

Abstract

BackgroundMyolipoma of soft tissue is an extremely rare benign tumor composed of mature adipose tissue and smooth muscle cells. It is found predominantly in women. The cytogenetic and molecular genetic features of myolipomas remain largely unexplored. Here we present the first cytogenetically analyzed myolipoma.MethodsCytogenetic and molecular genetic analyses were done on a myolipoma.ResultsG-banding analysis of short-term cultured cells from the myolipoma yielded a karyotype with a single clonal chromosome abnormality: 46,XX,t(9;12)(p22;q14). Fluorescence in situ hybridization experiments demonstrated that HMGA2 (in 12q14) was rearranged. Molecular genetic analysis showed that the translocation resulted in fusion of HMGA2 with the C9orf92 gene (from 9p22). The HMGA2-C9orf92 fusion transcript would code for a putative protein containing amino acid residues 1–94 of HMGA2 and 6 amino acid residues from the out-of-frame fusion with exon 4 of C9orf92.ConclusionThe pattern of HMGA2 rearrangement in the present case of myolipoma is similar to what is found in other benign connective tissue tumor types, including lipomas, i.e., disruption of the HMGA2 locus leaves intact exons which encode the AT-hook domains but separates them from the 3´-terminal part of the gene. Whether any genetic features differentiate myolipomas from regular lipomas with HMGA2-involvement is a question that cannot be answered until more cases of the former tumor type are subjected to genetic analysis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13000-016-0472-8) contains supplementary material, which is available to authorized users.

Recurrent Fusion of the Genes for High-mobility Group AT-hook 2 (HMGA2) and Nuclear Receptor Co-repressor 2 (NCOR2) in Osteoclastic Giant Cell-rich Tumors of Bone

“…This notwithstanding, many chromosomal rearrangements, such as balanced and unbalanced translocations, inversions, insertions, and deletions involving band 12q14 and targeting the HMGA2 gene have repeatedly been reported in lipomas and other benign neoplasms of connective tissues (40). In most cases, HMGA2 fuses out-of-frame with the 3'-end partner gene or with intergenic sequences (32,34,36,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). In these fusions, the part of the HMGA2 gene coding for the AT-hook domains, i.e., exons 1 to 3, is separated from the 3'-untranslated region which regulates HMGA2 transcription, resulting in expression and translation of a tumorigenic, truncated form of HMGA2 (54)(55)(56)(57)(58)(59)(60).…”

Mammary-type Myofibroblastoma with Leiomyomatous Differentiation: A Rare Variant with Potential Pitfalls

“…12 Recent genetic studies have shown an acquired chromosomal translocation, t(9;12)(p22;q14) occurring in myolipoma, resulting in fusion of the C9orf92 and HMGA2 genes; and, while studies are limited on myolipoma in general, no reports of 13q14 or RB1 loss have been published to date. 17,19 Numerous genetic studies of leiomyoma, on the other hand, have revealed that mutations in MED12 and HMGA2 may account for approximately 80-90% of all uterine leiomyomas. 20 Unlike their uterine counterparts, however, extrauterine leiomyomas infrequently harbor MED12 mutations, but may exhibit rearrangements of HMGA2 or PLAG1 .…”

Myolipoma

“…Cytogenetic alterations of HMGA2 have been reported in two myolipomas, and the majority of tumors tested have shown nuclear reactivity for HMGA2 (Hisaoka et al 2002;Panagopoulos et al 2016;Fukushima et al 2017).…”