{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T10:59:49Z","timestamp":1775473189882,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:00:00Z","timestamp":1693785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, <jats:italic>TP53<\/jats:italic> mutant or wild type, and non-WNT\/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the <jats:italic>CTNNB1<\/jats:italic> gene (85%\u201390%), and most remaining cases <jats:italic>of CTNNB1<\/jats:italic> wild type are thought to be caused by germline mutations in <jats:italic>APC<\/jats:italic>. So far, the frequencies of <jats:italic>CTNNB1<\/jats:italic> have been reported mainly in North American and European populations. The aim of this study was to report the frequency of <jats:italic>CTNNB1<\/jats:italic> mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and <jats:italic>CTNNB1<\/jats:italic> mutation analysis were performed by nCounter and Sanger sequencing, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WNT-activated medulloblastomas accounted for 15% (40\/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored <jats:italic>CTNNB1<\/jats:italic> mutations. <jats:italic>CTNNB1<\/jats:italic> wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the <jats:italic>CTNNB1<\/jats:italic> wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring <jats:italic>APC<\/jats:italic> germline variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We observed a lower incidence of <jats:italic>CTNNB1<\/jats:italic> mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that <jats:italic>CTNNB1<\/jats:italic> wild-type cases may exhibit <jats:italic>APC<\/jats:italic> germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2023.1237170","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T10:23:09Z","timestamp":1693822989000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population"],"prefix":"10.3389","volume":"13","author":[{"given":"Daniel Antunes","family":"Moreno","sequence":"first","affiliation":[]},{"given":"Murilo","family":"Bonatelli","sequence":"additional","affiliation":[]},{"given":"Augusto 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