TP53p.Arg337His geographic distribution correlates with adrenocortical tumor occurrence

Author(s)

Seidinger, Ana L. ; Caminha, Isabel P. ; Mastellaro, Maria J. ; Gabetta, Carmen S. ; Nowill, Alexandre E. ; Pinheiro, Vitoria R. P. ; Yunes, Jose A.

• Document type: Journal article
• Source: MOLECULAR GENETICS & GENOMIC MEDICINE; v. 8, n. 9, p. 9-pg., 2020-06-27.

Abstract

Background The p.Arg337His mutation of theTP53is the most frequent germline missense variant associated with cancer described so far in this gene. It is mainly found in the South and Southeastern regions of Brazil, where it has been associated with a high incidence of pediatric adrenocortical (ACT) and choroid plexus tumors. The frequency and geographic distribution of this mutation is largely unknown, except for the Parana State, where a mean prevalence of 0.27% was reported. In the present study, we developed a high-throughput method for p.Arg337His genotyping, what allowed us to determine the frequency and geographic distribution of this mutation in a cohort from the most populous state in Brazil. Methods Consecutive samples from 31,612 newborns from Sao Paulo State were screened for p.Arg337His. The allelic discrimination was done by real-time polymerase chain reaction (PCR) and the presence of haplotype A3 in carriers was examined by using allele-specific oligonucleotide PCR, followed by nested-PCR to detect the SNP rs9894946. Results We found 67 (0.21%) samples positive for this mutation. The highest p.Arg337His frequencies were found in the cities close to the boundary between Sao Paulo and Minas Gerais State. No association could be found between p.Arg337His and gender, ethnicity, premature birth or twinning. Remarkably, a trend was found between the geographic distribution of p.Arg337His carriers and occurrence of ACT. Conclusion We presented for the first time the p.Arg337His frequency among individuals unselected for any disease from a subset of the Sao Paulo State, the most populous in Brazil. The allele discrimination assay we presented here has proven to be a reliable and efficient method for high-throughput genotyping. ACT was found to be a good sentinel cancer to suppose p.Arg337His presence in our region. (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 Opportunities: Scholarships in Brazil - Doctorate