Original articleFusion of HMGA1 to the LPP/TPRG1 intergenic region in a lipoma identified by mapping paraffin-embedded tissues
Introduction
Ordinary lipoma frequently harbors rearrangement of the high mobility group AT-hook 2 gene (HMGA2) [1]. The lipoma preferred partner gene (LPP), located on chromosome band 3q27∼q28, is the most common fusion partner with HMGA2 on chromosome 12 [2], but has not been seen fused to HMGA1, a homologous gene to HMGA2 and located on chromosome band 6p21. HMGA2–LPP fusion has been reported in ∼25% of tumors with chromosome 12q13∼q15 aberrations [3]. Rearrangements of HMGA1 have been observed in a variety of benign tumors, including uterine leiomyomas [4], [5], [6], pulmonary chondroid hamartomas [6], [7], [8], [9], endometrial polyps [6], ordinary lipomas [6], [9], breast hamartomas [10], and spindle cell lipomas [11]. Kazmierczak et al. [9] reported HMGA1 rearrangements in a lipoma with t(3;6)(q27;p21). This finding suggested the involvement of LPP; however, no further investigation was conducted to confirm this impression. Here, we report the fusion of the HMGA1 locus to the intergenic region between the LPP and TPRG1 (tumor protein p63 regulated 1) loci in a lipoma with t(3;6).
Section snippets
Tumor sample
The tumor was classified according to established histological criteria [1]. At the time of the diagnosis, fresh tissue was available for conventional cytogenetic analysis but only a single block of formalin-fixed, paraffin-embedded tissue was available for molecular cytogenetic analysis. Two ordinary lipomas without chromosome 6p21 aberration were used as negative controls. This study was approved by the Mayo Clinic Institutional Review Board.
Conventional cytogenetic analysis
Conventional cytogenetic analysis was performed on
Histology
The patient was a 60-year-old woman with a 10.7-cm subcutaneous mass located on the left side of the anterior abdominal wall. Microscopic examination revealed a proliferation of mature adipocytes without cytologic atypia.
Conventional cytogenetic analysis
Cytogenetic analysis of the tumor demonstrated the following karyotype: 46,XX,t(3;6)(q27;p21.1)[20] (Fig. 1A).
Rearrangement of HMGA1, LPP, and HMGA2
Initial analysis with the HMGA1 break-apart probe set (i.e., the 5′-HMGA1 orange probe and the 3′-HMGA1 green probe) demonstrated an apparent balanced rearrangement of
Discussion
HMGA1 encodes for a chromatin remodeling protein structurally homologous to HMGA2[17]. In lipomas, HMGA1 aberrations are observed in less than 10% of cases [9], [18], [19], [20]. We have encountered an ordinary lipoma with the t(3;6)(q27;p21.1), which suggests the involvement of both HMGA1 and LPP, the latter being the most common HMGA2 partner gene observed in ordinary lipomas. A series of FISH experiments using custom-designed probes for both HMGA1 and LPP showed the fusion of HMGA1 to a
Acknowledgments
This work was funded by Fraternal Order of Eagles Foundation Award 237 and Mayo Clinic CR20 Award 14546.
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