Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The uterine leiomyoma variants harbored MED12 exon 2 mutations significantly less frequently than common leiomyomas (P=2.93 × 10(-8)).
|
23443020 |
2013 |
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 |
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 |
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 |
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 |
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 |
Similarly, MED12 mutation-positive leiomyomas displayed no additional recurrent changes.
|
23913526 |
2014 |
Fibroid Tumor
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The lack of mediator complex subunit 12 mutations in extrauterine leiomyomas and leiomyosarcomas indicates that these tumors arise through a different pathway, emphasizing the genetic heterogeneity of smooth muscle tumors.
|
23517922 |
2013 |
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 |
When we further examined HMGA2 expression in all leiomyomas and leiomyosarcomas, we found that HMGA2 overexpression was exclusively present in those leiomyomas with no MED12 mutation, accounting for 10.1% (18/178) of total leiomyomas and 40% (18/45) of non-MED12 mutant leiomyomas.
|
24390224 |
2014 |
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 |
Exome sequencing identified that the majority of leiomyomas display highly specific MED12 mutations.
|
25106763 |
2014 |
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 |
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 |
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 |
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, 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 |
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 |
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 |
We identified somatic MED12 mutations in 90% (9/10) of the adnexal leiomyomas.
|
29944972 |
2018 |
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 |
GeneticVariation
|
disease |
BEFREE |
The results confirm the occurrence of fibroid-type MED12 mutations in malignant uterine smooth muscle tumors thus suggesting a rare but existing leiomyoma-LMS sequence.
|
23225304 |
2013 |
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 |
Furthermore, the mutation spectrum of MED12 in the concurrent leiomyomas was noticeably different.
|
28693134 |
2017 |
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 |