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Comparative analysis between telomere length and clinical features of carriers of the germline p.R337H TP53 mutation

Grant number: 14/03279-9
Support type:Scholarships in Brazil - Master
Effective date (Start): June 01, 2014
Effective date (End): March 31, 2016
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Maria Isabel Alves de Souza Waddington Achatz
Grantee:Kelvin César de Andrade
Home Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
Associated scholarship(s):14/14319-1 - Comparative analysis between telomere length and clinical features of carriers of the germline TP53 p.R337H mutation, BE.EP.MS


Li-Fraumeni syndrome is a hereditary cancer predisposition syndrome related to germline TP53 mutations. Despite of being rare worldwide, it was verified in Brazil the high occurrence of a founder mutation in this gene, the p.R337H. This mutation, which occurs in the oligomerization domain of the p53 protein, differs from the others commonly described, since these latter are found in the DNA binding domain. In a subgroup of asymptomatic carriers of the p.R337H mutation, specific characteristics were observed, such as low frequency of metabolic changes and diseases which are typical of aging, besides a better fitness than general population. Due to these observations, it was possible to propose the first evidences that these individuals have genetic factors modulating cellular senescence. Given the interaction between the p53 protein, telomere pathway and senescence, the hypothesis of this project is that asymptomatic carriers of the p.R337H mutation will have longer telomeres when compared to both: carriers affected by cancer and control group (asymptomatic and without any described mutation). This fact would differentiate the asymptomatic p.R337H carriers from patients with other mutations in the TP53 gene who have shorter telomeres when compared to the population of corresponding age. Through analysis of telomere length, we will evaluate 40 patients positive for the p.R337H mutation, being 20 with cancer and 20 without cancer. In addition, these groups will be compared to 40 control individuals. This study will provide a better understanding of the biological consequences of the germline p.R337H TP53 mutation, as well as additional information about the characteristics of patients positive for one of the most prevalent mutations already described in the Brazilian population. (AU)