Researchers have identified a new cancer gene - one that is common to many cancers and affects the most basic regulation of our genes.
The new example - a gene on the X chromosome called UTX - is found in 10% of cases of multiple myeloma and 8% of esophageal cancers.
UTX plays a role in overall regulation of the activity of many genes and it is possible that other genes with similar roles will also be found to be involved in different tumor types. This is the first example of mutations in a gene of this functional class. The finding arose from a study of mutations in 4000 genes in kidney cancer.
"UTX is an important component of the transcriptional control machinery - it influences some of the most fundamental mechanisms controlling gene activity in our cells," explains Dr Andy Futreal, co-leader of the Cancer Genome Project at the Wellcome Trust Sanger Institute. "Unlike many cancer genes, UTX does not appear to be directly involved in cell division or cell death but in basic gene regulation and shows the depths to which cancers will plumb in order to get themselves ready to go."
The normal UTX protein modifies part of the structure holding DNA together in our cells. The composite DNA–protein structure, called chromatin, is not simply a scaffold, but plays an active role in controlling gene activity. The UTX protein alters a key organising subunit component of chromatin, called a histone. The protein is likely to be involved in both turning genes on and off, making it a key regulator of the yin-yang of gene control.
In the massive DNA sequencing study, the team found rare mutations of the UTX gene in clear cell renal cancer - a type of kidney cancer. When they expanded the search they found mutations in many cancer types - including one in ten multiple myeloma and one in twelve esophageal cancer cases.
"This work shows that mutations in genes with different functions can be found in human cancer through systematic approaches. These results indicate that cancer genes are not restricted to 'classical' roles of survival and cell proliferation, but can affect a variety of other cellular mechanisms," explains Professor Victor Velculescu, Associate Professor of Oncology and Director of Cancer Genetics from the Ludwig Center at Johns Hopkins and co-Director of Cancer Biology, at Johns Hopkins Kimmel Cancer Center. "UTX wouldn't have been found without this high-throughput type of study and indicates the type of novel findings we might expect from the International Cancer Genome Consortium."