Fibroid Tumor
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
We used tissue samples and clinical data of 108 patients with leiomyomas to analyze the relation between EPO mRNA expression and MED12 mutation.
|
30554729 |
2019 |
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 |
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 |
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 |
Unsupervised clustering of results from DNA methylation analyses segregates normal myometrium from fibroids and further segregates the fibroids into subtypes characterized by MED12 mutation or activation of either HMGA2 or HMGA1 expression.
|
31851934 |
2019 |
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 |
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 |
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 |
We identified somatic MED12 mutations in 90% (9/10) of the adnexal leiomyomas.
|
29944972 |
2018 |
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 |
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
This study confirmed the previously reported differences and discovered novel differentiating features for MED12-mutation-positive and -negative leiomyomas.
|
28432313 |
2017 |
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 |
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 |
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 in leiomyomas with bizarre nuclei were detected outside the hotspot region.
|
27363490 |
2016 |
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 |
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 |
This study provides insight into the intratumor heterogeneity of these tumors and suggests that a shared clonal origin is a common feature of leiomyomas that do not carry an MED12 mutation.
|
25964426 |
2015 |
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Together, our results show that the common human leiomyoma-associated MED12 variant can cause leiomyomas in mice via a gain of function that drives genomic instability, which is frequently observed in human leiomyomas.
|
26193636 |
2015 |
Fibroid Tumor
|
0.100 |
Biomarker
|
disease |
BEFREE |
The discovery of MED12 involvement in leiomyoma genesis has dramatically contributed to increasing our knowledge on leiomyomas, but many questions remain.
|
26037152 |
2015 |
Fibroid Tumor
|
0.100 |
Biomarker
|
disease |
BEFREE |
The recent discovery of somatic mutations involving mediator subunit complex 12 (MED12) or high-mobility group AT-hook 2 (HMGA2) in the majority of fibroids and the links to their pathophysiology were also significant advances.
|
26107781 |
2015 |
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 |
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.
|
25272295 |
2014 |
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 |
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 |