Amplification analysis of other genes at 12q13 (GLI, CHOP, HMGI-C and MDM2) in these 6 cases supports the view that CDK4 and MDM2 are independent targets for amplification, with variable amplification of the intervening region containing HMGI-C. Of 46 patients studied for both INK4A alterations and CDK4 amplification, the tumors in 22% contained one or the other.
His chromosomal inversion was found to truncate HMGA2, a gene that encodes an architectural factor involved in the etiology of many benign mesenchymal tumors and that maps to the 12q14.3 breakpoint.
The major differences in exDNA profiles between groups were: i) the level of GC-poor sequences increased during tumour development was reduced to that of healthy mice; ii) levels of sequences corresponding to tumour-associated genes Hmga2, Myc and Jun were reduced in the DNase I-treated group in comparison with non-treated mice; iii) 224 types of tandem repeat over-presented in untreated LLC-bearing mice were significantly reduced after DNase I treatment.
The expression of miR-370 was decreased by CXCL12 treatment in NFPAs. miR-370-3p was predicted and verified to target HMGA2 as a tumor suppressor gene.
MED12 mutations were the most common alterations in conventional and mitotically active leiomyomas and leiomyosarcomas, while leiomyomas with bizarre nuclei were most often FH deficient and cellular tumors showed frequent HMGA2 overexpression.
The xenograft tumor model was performed to examine the influence of the lncRNA FOXD2-AS1/miR-185-5p/HMGA2 network on the biological functions of glioma cells.
However, a reactivation of HMGA2 expression has been described for various malignant tumors and often correlates with the aggressiveness of the tumors.
HMGIC, a high-mobility-group protein gene encoding an architectural transcription factor, was recently identified as the target of gene fusion in a variety of human benign mesenchymal tumors; some of these events were chromosomal translocations involving 12q13-15.
Immunostaining revealed that the HMGIC protein was highly overexpressed particularly in the large polymorphic cells within the carcinomatous part of the tumor.
Rearrangements of chromosome arm 15q are rare but recurrent in conventional lipomas, a tumor type often showing deregulated expression of the HMGA2 gene.
This pattern of expression, restricted to nonendometrioid carcinomas and endometrial carcinosarcomas, reflects a role for high mobility group AT-hook 2 in endometrial carcinogenesis that is associated with aggressive phenotypes and points to its potential use as a marker to distinguish between endometrioid and nonendometrioid tumors.
The reason may be that HMGA2 promotes epithelial-mesenchymal transition (EMT) and the acquisition of tumor stem cell properties, yet the mechanism remains unclear.
The absence of the HMGA2-LPP fusion in small populations of tumors with a normal karyotype suggests the primary nature of chromosomal rearrangements in the development of PCH affected by those aberrations.