Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas
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...
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2021
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oai:doaj.org-article:651bc04a5fbc4ef3baa4c70aeaba289e2021-11-17T05:24:55ZWhole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas2234-943X10.3389/fonc.2021.740782https://doaj.org/article/651bc04a5fbc4ef3baa4c70aeaba289e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.740782/fullhttps://doaj.org/toc/2234-943XHuman 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.María González-TablasMaría González-TablasMaría González-TablasCarlos PrietoCarlos PrietoDaniel ArandiaDaniel ArandiaMaría Jara-AcevedoMaría Jara-AcevedoÁlvaro OteroÁlvaro OteroDaniel PascualDaniel PascualLaura RuízLaura RuízIván Álvarez-TwoseIván Álvarez-TwoseAndrés Celestino García-MonteroAndrés Celestino García-MonteroAndrés Celestino García-MonteroAndrés Celestino García-MonteroAlberto OrfaoAlberto OrfaoAlberto OrfaoAlberto OrfaoMaría Dolores TaberneroMaría Dolores TaberneroMaría Dolores TaberneroMaría Dolores TaberneroFrontiers Media S.A.articlemutational profileswhole exome sequencing (WES)NF2PTENcytogeneticsWHO grade 1 meningiomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021) |
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| topic |
mutational profiles whole exome sequencing (WES) NF2 PTEN cytogenetics WHO grade 1 meningioma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
mutational profiles whole exome sequencing (WES) NF2 PTEN cytogenetics WHO grade 1 meningioma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 María González-Tablas María González-Tablas María González-Tablas Carlos Prieto Carlos Prieto Daniel Arandia Daniel Arandia María Jara-Acevedo María Jara-Acevedo Álvaro Otero Álvaro Otero Daniel Pascual Daniel Pascual Laura Ruíz Laura Ruíz Iván Álvarez-Twose Iván Álvarez-Twose Andrés Celestino García-Montero Andrés Celestino García-Montero Andrés Celestino García-Montero Andrés Celestino García-Montero Alberto Orfao Alberto Orfao Alberto Orfao Alberto Orfao María Dolores Tabernero María Dolores Tabernero María Dolores Tabernero María Dolores Tabernero Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas |
| description |
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. |
| format |
article |
| author |
María González-Tablas María González-Tablas María González-Tablas Carlos Prieto Carlos Prieto Daniel Arandia Daniel Arandia María Jara-Acevedo María Jara-Acevedo Álvaro Otero Álvaro Otero Daniel Pascual Daniel Pascual Laura Ruíz Laura Ruíz Iván Álvarez-Twose Iván Álvarez-Twose Andrés Celestino García-Montero Andrés Celestino García-Montero Andrés Celestino García-Montero Andrés Celestino García-Montero Alberto Orfao Alberto Orfao Alberto Orfao Alberto Orfao María Dolores Tabernero María Dolores Tabernero María Dolores Tabernero María Dolores Tabernero |
| author_facet |
María González-Tablas María González-Tablas María González-Tablas Carlos Prieto Carlos Prieto Daniel Arandia Daniel Arandia María Jara-Acevedo María Jara-Acevedo Álvaro Otero Álvaro Otero Daniel Pascual Daniel Pascual Laura Ruíz Laura Ruíz Iván Álvarez-Twose Iván Álvarez-Twose Andrés Celestino García-Montero Andrés Celestino García-Montero Andrés Celestino García-Montero Andrés Celestino García-Montero Alberto Orfao Alberto Orfao Alberto Orfao Alberto Orfao María Dolores Tabernero María Dolores Tabernero María Dolores Tabernero María Dolores Tabernero |
| author_sort |
María González-Tablas |
| title |
Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas |
| title_short |
Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas |
| title_full |
Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas |
| title_fullStr |
Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas |
| title_full_unstemmed |
Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas |
| title_sort |
whole-exome sequencing reveals recurrent but heterogeneous mutational profiles in sporadic who grade 1 meningiomas |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/651bc04a5fbc4ef3baa4c70aeaba289e |
| work_keys_str_mv |
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