Prevalence of germline TP53 p.R337H mutation at metropolitan area of Campinas and surrounding cities

Author(s)

Isabel Pereira Caminha

• Document type: Doctoral Thesis
• Institution: Universidade Estadual de Campinas. Instituto de Biologia
• Defense date: 24 fev. 2015

Examining board members

Maria Isabel Alves de Souza Waddington Achatz; Juliana Godoy Assumpção; Louis Bernard Klaczko; Juliana Sampaio Farinaci

• Advisor: José Andrés Yunes

Abstract

The germline p.R337H mutation of TP53 gene is associated with high incidence of adrenocortical tumors (ACT) in South and Southeastern regions of Brazil, where evidence indicates the occurrence of founder effect. The high frequency of this mutation in Southern Brazil encouraged us to develop a suitable method for mutation detection on a large scale, aiming to determine the frequency of p.R337H in a population of the most populous state in Brazil, São Paulo. A novel method was developed in order to detect p.R337H mutation in samples collected on Guthrie card, using real time PCR. Genomic DNA samples from 34.344 newborns from a specific region of São Paulo State were screened for this germline mutation. Alelle-Specific-PCR and Nested-PCR Assays were used to verify the presence of the Brazilian founder p.R337H haplotype in newborn mutation carriers. Among the 34.344 screened samples, we found 75 carriers of the TP53 p.R337H mutation. This frequency (0,21%) is close to that found in Brazil Southern region. We identified the haplotype A3 in all patients in whom the sample was suitable for analysis. The distribution of the mutation was shown to be heterogeneous, being more abundant in cities bordering the south of Minas Gerais. Our data indicate that the frequency found in a population of the State of São Paulo is close to that found in other regions of Brazil. Furthermore, the presence of the founder haplotype in all carriers, support the hypothesis of founder effect. We developed an appropriate technology for large-scale screening, using samples collected on filter paper. The identification of patients at birth may increase the chances of early diagnosis, improving the prognosis of these patients and alerting family members about an increased susceptibility to other cancers. However, further studies are required, for example, to assess the occurrence of cancer in adult patients with the mutation as well as the psychological impact of a screening program in the healthy population and in most carriers, who do not develop the disease. (AU)

• FAPESP's process: 11/05657-2 - Prevalence and impact of TP53 R337H germinative mutation in the Metropolitan Region of Campinas
• Grantee: Isabel Pereira Caminha
• Support type: Scholarships in Brazil - Doctorate