In a uterine leiomyoma and a myxoid liposarcoma with translocations 12;14 and 12;16, the breakpoints in chromosome 12 could be localized to the HMGIC and CHOP regions, respectively.
Cells of one genetic subtype of UL, i.e., those with rearrangements of the high mobility AT-hook 2 protein gene (HMGA2), seem to be able to proliferate in vitro for many passages whereas tumor cells from the much more frequent MED12-mutated lesions barely survive even the first passages.
Whereas 70.0% (14/20) HMGA2-mutated fibroids made their appearance as solitary nodules, 85.5% (153/179) MED12-mutated fibroids occurred as multiple nodules as a rule of independent clonal origin, as reflected by different MED12 mutations.
By fluorescence in situ hybridization (FISH) we found the chromosome 12 translocation breakpoint to be mapping within the third intron of the HMGI-C gene also harboring the breakpoints of translocations involving 12q15 seen in uterine leiomyomas, lipomas, pleomorphic adenomas, and pulmonary chondroid hamartomas.
In two pulmonary chondroid hamartomas from different patients and one uterine leiomyoma with apparently normal karyotypes, we found identical RTVL-H 3' LTRs fused as ectopic sequences to exon 3 of HMGI-C.
Truncated transcripts were apparently predominant in roughly one-third of UL with chromosomal rearrangements affecting the HMGA2 locus, where they lead to a higher stability of its transcripts and subsequently contribute to the overexpression of the protein.
The tumor with the 12q14-15 aberration as the sole alteration and the leiomyoma with 12q14-15 rearrangement plus deletion of the long arm of chromosome 7 were shown to express HMGIC.
Myoid hamartoma of the breast may be pathogenetically related to benign connective tissue tumors with HMGA2 rearrangements, such as pulmonary hamartomas, lipomas, myolipomas, and leiomyomas.
A T/C SNP in intron 1 and exon 2 boundary of estrogen receptor (ER) alpha gene recognized by PvuII enzyme has been associated with several female pathologies like breast cancer, osteoporosis, endometriosis and fibroids in various ethnic groups.
Carriage of the ESR1IVS1-397 T/C (PvuII), COMT G158A, and the CYP17A 34T-->C SNPs is not associated with the susceptibility to uterine leiomyoma in a Caucasian population.
The purpose of this study was to analyze the effect of ERα-351 XbaI A/G, ERα-397 PvuII T/C, and progesterone receptor (PGR) PROGINS polymorphisms on the development of leiomyomas.
We aimed to elucidate the association of estrogen receptor alpha (ERalpha)-351 A>G (XbaI) and -397 T>C (PvuII) gene polymorphisms with endometriosis and leiomyoma.
In conclusion, there was an aberrant DNA methylation status in the promoter region of ER-alpha gene in uterine leiomyoma, which may be associated with high ER-alpha mRNA expression.
This study emphasizes the importance of considering FH mutation screening when gynecologists encounter families with multiple severe uterine leiomyoma cases.