{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:24:51Z","timestamp":1790807091979,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T00:00:00Z","timestamp":1593216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2011\/05657\u20102"],"award-info":[{"award-number":["2011\/05657\u20102"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["401991\/2010"],"award-info":[{"award-number":["401991\/2010"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The p.Arg337His mutation of the <jats:italic>TP53<\/jats:italic> is 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\u2010throughput 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Consecutive samples from 31,612 newborns from S\u00e3o Paulo State were screened for p.Arg337His. The allelic discrimination was done by real\u2010time polymerase chain reaction (PCR) and the presence of haplotype A3 in carriers was examined by using allele\u2010specific oligonucleotide PCR, followed by nested\u2010PCR to detect the SNP rs9894946.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 S\u00e3o 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We presented for the first time the p.Arg337His frequency among individuals unselected for any disease from a subset of the S\u00e3o 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\u2010throughput genotyping. ACT was found to be a good sentinel cancer to suppose p.Arg337His presence in our region.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1168","type":"journal-article","created":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T11:33:03Z","timestamp":1593257583000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["<i>TP53<\/i> p.Arg337His geographic distribution correlates with adrenocortical tumor occurrence"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-4649","authenticated-orcid":false,"given":"Ana L.","family":"Seidinger","sequence":"first","affiliation":[{"name":"Molecular Biology Laboratory Centro Infantil Boldrini Campinas S\u00e3o Paulo Brazil"},{"name":"Medical Genetics Department Faculty of Medical Sciences State University of Campinas Campinas S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel P.","family":"Caminha","sequence":"additional","affiliation":[{"name":"Integrated Center of Oncohematology Research in Childhood State University of Campinas Campinas S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Mastellaro","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Centro Infantil Boldrini Campinas S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen S.","family":"Gabetta","sequence":"additional","affiliation":[{"name":"Integrated Center of Oncohematology Research in Childhood State University of Campinas Campinas S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre E.","family":"Nowill","sequence":"additional","affiliation":[{"name":"Integrated Center of Oncohematology Research in Childhood State University of Campinas Campinas S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vit\u00f3ria R. 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