{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:54:02Z","timestamp":1791395642215,"version":"4.3.3"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"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:p>Human WHO grade 1 meningiomas are generally considered benign tumors; despite this, they account for \u224850% of all recurrent meningiomas. Currently, limited data exist about the mutational profiles of grade 1 meningiomas and patient outcome. We investigated the genetic variants present in 32 WHO grade 1 meningiomas using whole exome sequencing, and correlated gene mutational profiles with tumor cytogenetics and patient outcome. Overall, WHO grade 1 meningiomas harbored numerous and heterogeneous genetic variants, which most frequently affected the <jats:italic>NF2<\/jats:italic> (47%) gene and to a less extent the <jats:italic>PNMA6A<\/jats:italic> (22%), <jats:italic>TIGD1<\/jats:italic> (16%), <jats:italic>SMO<\/jats:italic> (13%), <jats:italic>PTEN<\/jats:italic> (13%), <jats:italic>CREG2<\/jats:italic> (9%), <jats:italic>EEF1A1<\/jats:italic> (6%), <jats:italic>POLR2A<\/jats:italic> (6%), <jats:italic>ARID1B<\/jats:italic> (3%), and <jats:italic>FAIM3<\/jats:italic> (3%) genes. Notably, non-synonymous genetic variants of <jats:italic>SMO<\/jats:italic> and <jats:italic>POLR2A<\/jats:italic> were restricted to diploid meningiomas, whereas <jats:italic>NF2<\/jats:italic> mutations were only found among tumors that showed -22\/22q<jats:sup>\u2500<\/jats:sup> (with or without a complex karyotype). Based on <jats:italic>NF2<\/jats:italic> mutations and tumor cytogenetics, four genetic profiles were defined with an impact on patient recurrence-free survival (RFS). These included (1) two good-prognosis tumor subgroups\u2014diploid meningiomas (n=9) and isolated -22\/22q<jats:sup>\u2500<\/jats:sup> associated with <jats:italic>NF2<\/jats:italic> mutation (n=7)\u2014with RFS rates at 10 y of 100%; and (2) two subgroups of poor-prognosis meningiomas\u2014isolated -22\/22q<jats:sup>\u2500<\/jats:sup> without <jats:italic>NF2<\/jats:italic> mutation (n=3) and tumors with complex karyotypes (n=11)\u2014with a RFS rate at 10 y of 48% (p=0.003). Our results point out the existence of recurrent but heterogeneous mutational profiles in WHO grade 1 meningiomas which have an impact on patient outcome.<\/jats:p>","DOI":"10.3389\/fonc.2021.740782","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T06:29:43Z","timestamp":1637130583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 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