They often carry chromosome aberrations involving 12q13~15 leading to rearrangements of the HMGA2 gene in 12q14.3, with breakpoints occurring within or outside of the gene.
In a total of 80 cytogenetically characterized fibroids from 50 patients, we were not only able to confirm the frequent occurrence of MED12 mutations but also to stratify two mutually exclusive pathways of leiomyomagenesis with either rearrangements of HMGA2 reflected by clonal chromosome abnormalities affecting 12q14~15 or by mutations affecting exon 2 of MED12.
There are only a few reports of the cytogenetic abnormalities in the pleomorphic adenomas (PA) that arise in children, and even less information regarding the pleomorphic adenoma gene 1 (PLAG1) and high motility group A2 (HMGA2 ) histochemical staining in PAs, or their correlation with histologic types (stromal vs epithelial predominance).
The significant (P < 0.05) overexpression of HMGA2 also in the group of fibroids without chromosomal aberrations of the 12q14-15 region suggests a general role of HMGA2 in the development of the disease.
Well-differentiated liposarcomas (WDLPS) classically contain high-level amplification of 12q14-15 sequences, including the MDM2 and CDK4 genes, while lipomas are characterized by simple structural chromosome aberrations often involving HMGA2 at 12q15.
As for a mechanism explaining this observation, it can be suggested that breakpoints of chromosomal aberrations not directly disrupting HMGIC may induce small genomic alterations in their vicinity and thus facilitate abnormal splicing.
These HMGIC aberrations are caused by characteristic structural chromosomal aberrations, either visible by conventional cytogenetics or as cryptic abnormalities.
The developmentally regulated HMGIC gene, which encodes an architectural transcription factor, has recently been linked to the pathogenesis of benign solid tumors with chromosome aberrations involving 12q13-15.
HMGIC expressed in a uterine leiomyoma with a deletion of the long arm of chromosome 7 along with a 12q14-15 rearrangement but not in tumors showing del(7) as the sole cytogenetic abnormality.
Because of these cytogenetic aberrations the HMGI-C gene (HGMW-approved symbol HMGIC) becomes rearranged, with most of the breakpoints located in the large intron 3.
Recently, we identified rearrangements of the HMGI-C gene within the third or fourth intron as the molecular mechanism underlying most of these chromosomal aberrations.