Genetic mechanism behind fibroid development discovered

Researchers have identified that variants in genes responsible for DNA packing in the cell, could lead to the development of fibroids.

Fibroids, also known as uterine leiomyoma, are benign tumours that grow in the uterine wall and can cause symptoms such as severe menstrual bleeding, pain and infertility. They are a leading cause of hysterectomy globally. While some genetic drivers were already understood to play a role in the development of fibroids, a team of researchers at the University of Helsinki and Helsinki University Hospital in Finland looked at fibroids with no known genetic cause. Their results published in Nature revealed a potential mechanism behind the development of fibroids that had not been understood before.

Dr Zehra Ordulu who was not involved in the research, wrote in Nature: 'Uterine leiomyomas affect millions of women and cost more than US$1 billion in health care annually in the United States. A comprehensive understanding of the genomic underpinnings of the distinct molecular subgroups of uterine leiomyomas might eventually inform clinical decision-making, from diagnosis to therapy.'

Researchers characterised 2263 fibroid tumours from 728 women into subgroups according to the genetic variants they displayed. While the majority of the fibroids could be categorised according to three previously defined genetic subgroups, the researchers found a previously uncharacterised subgroup of fibroid tumours with variations in genes that are involved in the packing of DNA in the cell. Specifically, the genes affected the genetic code for the SRCAP complex, which is involved in histone activity in the cell.

They then discovered that these gene variants could be an important hereditary risk factor for the development of fibroids, by analysing the genomes of women whose data was stored in the UK Biobank. Researchers found that hereditary mutations in YEATS4 and ZNHIT1, which both code for part of the SRCAP complex, predisposed women to developing fibroids.

Variations in these genes led to changes in chromatin structure, causing changes in the regulation of the expression of genes in uterine tissue, including tumour-driving genes, revealing a potential driver for the development of fibroids.

Professor Lauri Aaltonen, senior author on the paper said: 'In particular, genes that are poised to frequently turn on and off seem affected in fibroids. Thus, disturbances in genes that need to be poised to change expression level might harm the uterus more easily than other organs. Some of the overexpressed genes might provide clues for development of new fibroid treatment options'.

While more research is needed into the underlying mechanisms of how these mutations lead to the development of fibroids, the results also open up potential new ways to treat fibroids and for genetic counselling of those affected.