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Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas
Ist Teil von
Frontiers in oncology, 2021-11, Vol.11, p.740782-740782
Ort / Verlag
Frontiers Media S.A
Erscheinungsjahr
2021
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
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
NF2
(47%) gene and to a less extent the
PNMA6A
(22%),
TIGD1
(16%),
SMO
(13%),
PTEN
(13%),
CREG2
(9%),
EEF1A1
(6%),
POLR2A
(6%),
ARID1B
(3%), and
FAIM3
(3%) genes. Notably, non-synonymous genetic variants of
SMO
and
POLR2A
were restricted to diploid meningiomas, whereas
NF2
mutations were only found among tumors that showed -22/22q
─
(with or without a complex karyotype). Based on
NF2
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
─
associated with
NF2
mutation (n=7)—with RFS rates at 10 y of 100%; and (2) two subgroups of poor-prognosis meningiomas—isolated -22/22q
─
without
NF2
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.