Genetic Mutations Located in Urothelial Carcinoma

Genetic tests are being designed to allow the easy, early, accurate diagnosis of bladder cancer, and developing therapies that recognize these mutations.

Whole-exome sequencing of the genomic DNA from tissue samples led to the discovery of mutation in the gene that encodes for ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX) protein.

A team from the University of Colorado (Denver, CO, USA) in partnership with universities in China and Denmark reports the first genetic sequencing of urothelial (transitional) carcinoma, the most prevalent type of bladder cancer. In addition, the mutations the team found are similar to those recently discovered in a host of other cancers, implying a possible common denominator in the cause of cancer in general. Specifically, in 57 of 97 patients (59%), with urothelial carcinoma, the team found mutations in genes responsible for chromatin remodeling, which is the process of packaging DNA for easy duplication during cell division.

Chromatin describes the genetic contents of a cell's nucleus including the cell's DNA and the proteins that mold its arrangement inside the cell. These proteins arrange DNA loosely so that its inner parts are accessible and available for use. In preparation for cell division, these proteins in the cell's chromatin constrict DNA into a tight package for efficient duplication. In the development of bladder cancer, the study showed that chromatin remodeling is an important link.

Dan Theodorescu, MD, PhD, director the University of Colorado Cancer Center and an author of the work, said," The discovery of mutation in the UTX gene and seven similar chromatin remodeling genes is a major step toward genetic testing and treatment of bladder cancer". UTX has been linked with histone demethylation, a potential means of regulating cellular metabolism. The study also provides the first-ever overview of the genetic basis of urothelial bladder cancer and implicates chromatin remodeling in its cause. The study was published in August 7, 2011, in Nature Genetics.

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