TP53 p.Arg337His geographic distribution correlates with adrenocortical tumor occurrence

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• The TP53 p.Arg337His mutation is a frequent germline missense variant associated with cancer.
• This mutation is prevalent in Brazil, linked to pediatric adrenocortical tumors (ACT) and choroid plexus tumors.
• Its frequency and geographic distribution were largely unknown outside Parana State.

Purpose of the Study:

• To determine the frequency and geographic distribution of the p.Arg337His mutation in São Paulo State, Brazil.
• To develop and validate a high-throughput genotyping method for the p.Arg337His mutation.

Main Methods:

• Screened 31,612 newborn samples from São Paulo State for the p.Arg337His mutation.
• Utilized real-time polymerase chain reaction (PCR) for allelic discrimination.
• Employed allele-specific oligonucleotide PCR and nested-PCR for haplotype and SNP analysis.

Main Results:

• Identified the p.Arg337His mutation in 67 (0.21%) newborns.
• Observed highest mutation frequencies in cities near the São Paulo-Minas Gerais border.
• Found a trend associating p.Arg337His carriers with adrenocortical tumor occurrence.

Conclusions:

• This study provides the first p.Arg337His frequency data for unselected individuals in São Paulo State.
• The developed allele discrimination assay is a reliable and efficient high-throughput genotyping method.
• Adrenocortical tumors may serve as a sentinel for p.Arg337His presence in the region.