A single stem cell mutation triggers fibroid tumours
A mutation in MED12 gene found in majority of uterine fibroid tissues
- Date : 07 May 2012
- Topic : Personalised medicine
Fibroid uterine tumours cause irregular bleeding, anaemia, pain and infertility. Despite the high prevalence of the tumours, which occur in 60% of women by age 45, the molecular cause has been unknown.
New preclinical research has for the first time identified the molecular trigger of the tumour, a single stem cell that develops a mutation, starts to grow uncontrollably and activates other cells to join its frenzied expansion.
According to Dr Serdar Bulun, the chair of obstetrics and gynaecology at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital, Chicago, USA, the stem cells make up only low percentage of the cells in the tumour, yet they are the essential drivers of its growth.
The paper is published in the journal PLoS ONE, and Dr Masanori Ono, a post-doctoral student in Bulun's lab, is the lead author.
Tumours originating from the fibroid stem cell population are larger compared to tumours initiated with the main cell population
The stem cell initiating the tumour carries a mutation in the MED12 gene. Recently, mutations in this gene have been reported in the majority of uterine fibroid tissues. Once the mutation kicks off the abnormal expansion, the tumours grow in response to steroid hormones, particularly progesterone.
For the study, researchers examined the behaviour of human fibroid stem cells when grafted into a mouse, a novel model initiated by Northwestern scientist Takeshi Kurita, a research associate professor of obstetrics and gynaecology. The most important characteristic of fibroid stem cells is their ability to generate tumours. Tumours originating from the fibroid stem cell population grew 10 times larger compared to tumours initiated with the main cell population, suggesting a key role of these tumour stem cells is to initiate and sustain tumour growth.
Understanding how this mutation directs the tumour growth gives researchers a new direction to develop therapies. The study was supported by the USA National Institutes of Health Grant 34 NIH/NICHD 5P01HD057877, 1R01HD064402, NIH/NCI 1R01CA154358.
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