New cancer gene identified by Trust-funded research

30 March 2009

Mutations in the UTX gene, which regulates the activity of other genes, have been found in many different types of cancer, according to a study funded by the Wellcome Trust. The finding offers a new avenue for research that could lead to new cancer treatments.

In the study, researchers on the Cancer Genome Project based at the Wellcome Trust Sanger Institute in Hinxton, Cambridge, looked for UTX mutations in 1390 samples of cancer tissue.

They found rare mutations in one type of kidney cancer, clear cell renal cancer. Further analysis revealed other UTX mutations in one in ten multiple melanoma cases and one in twelve oesophageal cancer cases.

The UTX gene - found on the X chromosome - is involved in the function of histones, proteins that our DNA winds around in our cells to form a structure called chromatin. This helps to hold the DNA together and control gene activity.

Mutations in UTX disrupt the function of the histones, which may well affect gene regulation and hence lead to cancer.

The researchers showed that they could slow down the growth of cells lacking a functional UTX gene by reintroducing a normal copy of UTX.

"Unlike many cancer genes, UTX does not appear to be directly involved in cell division or cell death but in basic gene regulation," said Dr Andy Futreal, Co-Head of the Cancer Genome Project.

"UTX is an important component of the transcriptional control machinery: it influences some of the most fundamental mechanisms controlling gene activity in our cells."

UTX differs from other cancer genes in that changes to it cause cancer by affecting not the DNA code directly, but the associated proteins and chemical tags - known as epigenetic changes.

"This is a genetic change with consequences at the level of epigenetic regulation," said Professor Mike Stratton, Co-Head of the Cancer Genome Project. "When we look at cancers, a substantial proportion of the epigenetic disregulation may well have a genetic basis."

Image: Human chromosomes, histones (pink) and kinetochores at the metaphase stage of mitosis.

Credit: Laura Trinkle-Mulcahy, Wellcome Images

Reference

Van Haaften G et al. Somatic mutations of the histone H3K27 demethylase, UTX, in human cancer. Nat Genet 29 March 2009 [epub ahead of print].