Urothelial (transitional) bladder carcinoma, the most common type of bladder cancer, has mutations in genes that function in chromatin remodeling, affecting the way DNA is packaged, duplicated, and processed during cell division. Gui et al from China examined this issue in a study just published online in Nature Genetics. Common chromatin remodeling genes include UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A, and CHD6. The study highlighted certain missense and nonsense mutations, particularly with the UTX gene, suggesting its role in tumors of low stages and grades of transitional cell carcinoma.
Of the 97 patients in the study with transitional bladder cancer, 59% were found to have mutations. Chromatin is modified and regulated during post-translational modifications of the histone tails through acetylation, methylation, and phosphorylation. Moreover, the orderly function of nuclear processes depends on the proper state of chromatin because for example histone-DNA interactions are altered by ATP-dependent chromatin remodeling factors, allowing the nucleosomal DNA to function coherently with interacting proteins.
The researchers suggest that such discoveries hold the potential for creating genetic tests for quick and early diagnosis of bladder cancer. According to the American Bladder Cancer Society, over 70,000 cases of bladder cancer are diagnosed annually in the United States.
Sources:
- Gui Y, Guo G, Huang Y, et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder [published online ahead of print August 7, 2011]. Nature Genetics.
- Howlader N, Noone AM, Krapcho M, et al, eds. SEER Cancer Statistics Review 1975-2008. National Cancer Institute. Bethesda, MD. http://seer.cancer.gov/csr/1975_2008/.