The 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.
Our data therefore show that a subset of soft tissue osteochondromas shares pathogenetic involvement of HMGA2 with lipomas, leiomyomas and other benign connective tissue neoplasms.
Further cytogenetic studies of pediatric lipoma would be useful to determinate whether some partner genes of HMGA2, such as NFIB, may have a specific role in the early onset of these tumors.
The fact that the examined osteochondrolipoma had a t(12;18) and a HMGA2-SETBP1 fusion identical to the findings in the much more common ordinary lipomas, underscores the close developmental relationship between the two tumor types.
Rapid amplification of cDNA ends (RACE) PCR experiments revealed that one lipoma contained a fusion of the HMGA2 3' untranslated region (UTR) to a genomic area downstream of the DYRK2 locus on 12q15; the second lipoma showed a fusion of the HMGA2 3' UTR to a genomic sequence upstream of the DCN locus on 12q21.
Ninety-eight cases of lipoma were analyzed for the possible expression of HMGA2-LPP and LPP-HMGA2 fusion genes using a reverse-transcription polymerase chain reaction method.
Reverse-transcriptase polymerase chain reaction followed by sequencing analysis confirmed the presence of the HMGA2-LPP fusion gene, a characteristic and the most common fusion product found in lipoma.
We have identified an in-frame fusion of the first three exons of HMGA2 with exon 6 of MSRB3 (12q14.3) and exons 8 and 9 of NFIB by using 3'RACE-PCR in a case of superficial lipoma.
Moreover, because some features, such as overexpression of HMGA2, are shared by both lipomas and WDLPS, it has been hypothesized that lipomas and WDLPS may form a genetic and morphological continuum.
The lipoma preferred partner (LPP) gene is the most frequent translocation partner of HMGA2 in a subgroup of lipomas, which are benign tumors of adipose tissue.
In the present study, two cases of lipoma with rearrangements of 9p22-24 and 12q15 were analyzed by reverse transcription polymerase chain reaction to find out if HMGA2/NFIB was also present in lipoma.
Northern blot hybridizations of the lipoma cell line Li-14 revealed the expression of five additional HMGA2 transcripts consisting of exons 1 to 3 but not exons 4 to 5 besides the full-length HMGA2a transcript.
HMGA2, not expressed in normal subjects, is implicated in benign solid tumors such as lipomas, leiomyomas, and other rare tumors of mesenchymal origin.
Benign mesenchymal neoplasms associated with rearrangements of the DNA architectural factor gene HMGIC on chromosome 12 include lipomas, uterine leiomyomata, pulmonary chondroid hamartomas, endometrial polyps, salivary gland pleomorphic adenomas, and breast fibroadenomas.
However, HMGI-C and HMGI(Y) dysregulation as a result of specific rearrangements involving 12q15 and 6p21, the respective chromosomal sites in which the HMGI-C and HMGI(Y) genes are located, is also identified in a variety of common benign mesenchymal tumors, such as lipomas and uterine leiomyomata.