Brazilian Story of the R337H p53 Mutation

Abstract

The p53 tumor suppressor is an evergreen of molecular oncology. Since its discovery in 1979, it has been subjected to intensive investigation. The p53 protein is composed of "only" 393 amino acid residues, and function of almost each of them has been addressed in detail. Somatic mutations are extremely frequent, they can be found almost in each of the p53 codons and in all types of tumors. Inherited p53 mutations are rare but very penetrant, and they are typically associated with development of a broad spectrum of tumors. However, in 2001, the p53 research provided an unexpected discovery: the R337H allele was found in southern Brazil. This allele was atypically associated with only one type of tumor -  childhood adrenocortical carcinoma and it exhibited low penetrance. Therefore, new data on functioning and impact of the R337H mutation were highly desired. The results obtained during a few following years helped to elucidate not only this specific p53 variant but also provided insight into general principles of mutant p53 variants function. It also turned out that all R337H alleles that are very frequent in southern Brazil originate from one common ancestor. Key words: Li Fraumeni syndrome -  adrenocortical carcinoma -  p53 gene - R337HPráce byla podpořena grantem IGA MZ ČR č. NT/13784-4/2012. This study was supported by grant of Internal Grant Agency of the Czech Ministry of Health No. NT/13784-4/2012. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE "uniform requirements" for biomedical papers.Submitted: 28. 4. 2014Accepted: 19. 5. 2014.