Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability.

Uterine leiomyomas (ULs) are benign tumors that are a major burden to women's health. A genome-wide association study on 15,453 UL cases and 392,628 controls was performed, followed by replication of the genomic risk in six cohorts. Effects of the risk alleles were evaluated in view of molecular and clinical characteristics.

Global metabolomic profiling of uterine leiomyomas.

Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas.

Methods: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy.

Primary inferior vena cava smooth muscle tumor with diffuse bizarre giant nuclei and low mitotic rate: a nomenclatural conundrum.

A male patient with obstructive jaundice was found to have an incidental nodule within the inferior vena cava (IVC), below the level of the renal vein, on abdominal imaging. At the time of the Whipple's procedure for pancreatic adenocarcinoma, the IVC mass measuring 3.4×2.

Multiple clinical characteristics separate MED12-mutation-positive and -negative uterine leiomyomas.

Up to 86% of uterine leiomyomas harbour somatic mutations in mediator complex subunit 12 (MED12). These mutations have been associated with conventional histology, smaller tumour size, and larger number of tumours within the uterus. Prior studies, with limited sample sizes, have failed to detect associations between other clinical features and MED12 mutations.

MED12 mutations and FH inactivation are mutually exclusive in uterine leiomyomas.

Background: Uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer (HLRCC) patients are driven by fumarate hydratase (FH) inactivation or occasionally by mediator complex subunit 12 (MED12) mutations. The aim of this study was to analyse whether MED12 mutations and FH inactivation are mutually exclusive and to determine the contribution of MED12 mutations on HLRCC patients' myomagenesis.

Methods: MED12 exons 1 and 2 mutation screening and 2SC immunohistochemistry indicative for FH deficiency was performed on a comprehensive series of HLRCC patients' (122 specimens) and sporadic (66 specimens) tumours.

Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers.

Uterine leiomyomas are common benign smooth muscle tumors that impose a major burden on women's health. Recent sequencing studies have revealed recurrent and mutually exclusive mutations in leiomyomas, suggesting the involvement of molecularly distinct pathways. In this study, we explored transcriptional differences among leiomyomas harboring different genetic drivers, including high mobility group AT-hook 2 (HMGA2) rearrangements, mediator complex subunit 12 (MED12) mutations, biallelic inactivation of fumarate hydratase (FH), and collagen, type IV, alpha 5 and collagen, type IV, alpha 6 (COL4A5-COL4A6) deletions.

Clonally related uterine leiomyomas are common and display branched tumor evolution.

Uterine leiomyomas are extremely frequent benign smooth muscle tumors often presenting as multiple concurrent lesions and causing symptoms such as abnormal menstrual bleeding, abdominal pain and infertility. While most leiomyomas are believed to arise independently, a few studies have encountered separate lesions harboring identical genetic changes, suggesting a common clonal origin. To investigate the frequency of clonally related leiomyomas, genome-wide tools need to be utilized, and thus little is known about this phenomenon.

MED12 mutation frequency in unselected sporadic uterine leiomyomas.

Objective: To determine the frequency of mediator complex subunit 12 (MED12) mutations in well-documented, prospectively collected, unselected series of sporadic uterine leiomyomas to better understand the contribution of MED12 mutations in leiomyoma genesis.

Design: Mutation analysis of two prospectively collected sample series.

Setting: Department of gynecology in university hospital and medical genetics research laboratory.

Genomics of uterine leiomyomas: insights from high-throughput sequencing.

Uterine leiomyomas are benign smooth-muscle tumors of extremely low malignant potential. Early work utilizing classical cytogenetics revealed that a subset of uterine leiomyomas harbor recurrent chromosomal rearrangements, such as translocations affecting the HMGA2 gene. Our understanding of the genetics of many tumor types has deepened remarkably with the emergence of next-generation sequencing technologies.

Characterization of uterine leiomyomas by whole-genome sequencing.

Background: Uterine leiomyomas are benign but affect the health of millions of women. A better understanding of the molecular mechanisms involved may provide clues to the prevention and treatment of these lesions.

Methods: We performed whole-genome sequencing and gene-expression profiling of 38 uterine leiomyomas and the corresponding myometrium from 30 women.

MED12 exon 2 mutations are common in uterine leiomyomas from South African patients.

Uterine leiomyomas, or fibroids, are extremely common tumors. Regardless of their benign nature, fibroids can cause considerable morbidity. Women with African ancestry have a threefold increased risk of developing uterine leiomyomas with a greater symptom severity when compared to white women.