|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
MED12 mutations were equally distributed among karyotypically normal and abnormal uterine leiomyomas and were identified in leiomyomas from both black and white American women.
|
22428002 |
2012 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
MED12 mutations in leiomyomas with bizarre nuclei were detected outside the hotspot region.
|
27363490 |
2016 |
|
Fibroid Tumor
|
0.100 |
Biomarker
|
disease |
BEFREE |
MED12-negative leiomyomas contain copy number alterations involving the Mediator complex subunits such as MED8, MED18, CDK8, and long intergenic nonprotein coding RNA340 (CASC15), which may affect the Mediator architecture and/or its transcriptional activity.
|
27889101 |
2017 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
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.
|
28592321 |
2017 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
MED12 mutations in the fibroids were screened by Sanger sequencing. iTRAQ was used to label the peptides in small-, medium-, and large-sized fibroid samples of annotated MED12 mutation from the same patient.
|
29730954 |
2019 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Although this is the lowest mutation frequency reported so far, MED12 mutations are associated with fibroid pathogenesis in the studied population.
|
26298726 |
2016 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Among uterine smooth muscle tumours, MED12 mutations are frequently present in conventional leiomyomas, but are significantly less common in histological variants of leiomyoma and leiomyosarcoma.
|
23347103 |
2013 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Exome sequencing identified that the majority of leiomyomas display highly specific MED12 mutations.
|
25106763 |
2014 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, the mutation spectrum of MED12 in the concurrent leiomyomas was noticeably different.
|
28693134 |
2017 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Genetic sequencing of tissue samples revealed MED12 alterations in 39 of 65 fibroids (60%) from 14 patients.
|
29244110 |
2018 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here, we observed that overexpression of HMGA2 mRNA in tumors measured by quantitative PCR and compared to myometrium is a common phenomenon in fibroids and is frequently associated with MED12 mutations.
|
30017537 |
2018 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Herein, we determined the frequency of MED12 gene exon 2 somatic mutations in 143 fibroid tumors from a total of 135 women from the Southern United States and in 50 samples of the adjacent myometrium using PCR amplification and Sanger sequencing.
|
25325994 |
2015 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
However, G>A transitions of nucleotides c.130 or c.131 correlate with a significantly larger size of the fibroids compared to other MED12 mutations thus explaining the high prevalence of the former mutations among clinically detectable fibroids.
|
22223266 |
2012 |
|
Fibroid Tumor
|
0.100 |
PosttranslationalModification
|
disease |
BEFREE |
However, genetic alterations (especially MED12 and HMGA2) and involvement of epigenetic mechanisms (DNA methylation, histone modifications, and microRNA) in leiomyoma provide the clue of initiator of this tumor.
|
23557758 |
2013 |
|
Fibroid Tumor
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Immunoblotting studies demonstrated MED12 protein expression in 100% of leiomyomas (13) and leiomyosarcomas (20), irrespective of MED12 exon 2 mutation status or histological grade.
|
23222489 |
2013 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In contrast to usual-type leiomyoma with a high frequency of MED12 mutations, no MED12 mutations were found in any HLM.
|
30292626 |
2019 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In contrast, MED12 mutations were extremely common in ULM and MALM (> 74%) but were significantly less common (< 15%) in CLM, ALM, STUMP, and LMS (P < .01).
|
24986214 |
2014 |
|
Fibroid Tumor
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Interestingly all classical leiomyomas exhibit MED12 protein expression while 40% of atypical leiomyomas, 50% of STUMP and 80% of leiomyosarcomas (among them the two mutated ones) do not express MED12.
|
22768200 |
2012 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Most genetically mutated tumors (27/30; 90%) demonstrated only one type of genetic change, highlighting that even single allele change in MED12 can have profound impact in transforming the normal uterine myometrium to leiomyomas.
|
30619444 |
2018 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Mutational analysis of the MED12 gene, performed on 36 UL samples, revealed that 12 leiomyomas (33.4%) exhibited heterozygous missense mutations in codon 44 of exon 2 of the MED12 gene, four leiomyomas (11.1%) showed internal in-frame deletions, and two leiomyomas (5.5%) exhibited deletions involving intron 1-exon 2 junction, which caused a predicted loss of the splice acceptor.
|
25015674 |
2014 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Our results confirm the findings of similar recent studies and further show that pelvic and retroperitoneal leiomyomas harbor an increased frequency of MED12 mutations (34%) as compared with other extrauterine sites (0%; P = 0.0006), and that histologically unremarkable adjacent myometrium can harbor similar MED12 mutations.
|
24196187 |
2014 |
|
Fibroid Tumor
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
RAD51 paralog B (RAD51B), the preferential translocation partner of HMGA2, was up-regulated in MED12 mutant lesions, suggesting a role for this gene in the genesis of leiomyomas.
|
26787895 |
2016 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Rather, a 51-nucleotide deletion mutation including partial exon 2 of mediator complex subunit 12 (MED12), a gene commonly mutated in leiomyoma, breast fibroadenoma and phyllodes tumor, was identified.
|
29629977 |
2019 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Similarly, MED12 mutation-positive leiomyomas displayed no additional recurrent changes.
|
23913526 |
2014 |
|
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The DEGs in the MED12 mutation and wild-type leiomyoma samples, and common DEGs were defined as group A, B and C. Gene Ontology (GO) and pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery online tool.
|
29568968 |
2018 |