AUTHOR=González-Tablas María , Prieto Carlos , Arandia Daniel , Jara-Acevedo María , Otero Álvaro , Pascual Daniel , Ruíz Laura , Álvarez-Twose Iván , García-Montero Andrés Celestino , Orfao Alberto , Tabernero María Dolores 

TITLE=Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.740782

DOI=10.3389/fonc.2021.740782

ISSN=2234-943X

ABSTRACT=<p>Human WHO grade 1 meningiomas are generally considered benign tumors; despite this, they account for ≈50% 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 <italic>NF2</italic> (47%) gene and to a less extent the <italic>PNMA6A</italic> (22%), <italic>TIGD1</italic> (16%), <italic>SMO</italic> (13%), <italic>PTEN</italic> (13%), <italic>CREG2</italic> (9%), <italic>EEF1A1</italic> (6%), <italic>POLR2A</italic> (6%), <italic>ARID1B</italic> (3%), and <italic>FAIM3</italic> (3%) genes. Notably, non-synonymous genetic variants of <italic>SMO</italic> and <italic>POLR2A</italic> were restricted to diploid meningiomas, whereas <italic>NF2</italic> mutations were only found among tumors that showed -22/22q<sup>─</sup> (with or without a complex karyotype). Based on <italic>NF2</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—diploid meningiomas (n=9) and isolated -22/22q<sup>─</sup> associated with <italic>NF2</italic> mutation (n=7)—with RFS rates at 10 y of 100%; and (2) two subgroups of poor-prognosis meningiomas—isolated -22/22q<sup>─</sup> without <italic>NF2</italic> mutation (n=3) and tumors with complex karyotypes (n=11)—with 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.</p>