Oncotarget

Research Papers:

New insights into the genomic landscape of meningiomas identified FGFR3 in a subset of patients with favorable prognoses

Aysha AlSahlawi, Rasha Aljelaify, Amna Magrashi, Mariam AlSaeed, Amal Almutairi, Fatimah Alqubaishi, Abdulellah Alturkistani, Abdullah AlObaid, Mohamed Abouelhoda, Latifa AlMubarak, Nada AlTassan and Malak Abedalthagafi _

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Oncotarget. 2019; 10:5549-5559. https://doi.org/10.18632/oncotarget.27178

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Abstract

Aysha AlSahlawi1,2,3,*, Rasha Aljelaify1,4,*, Amna Magrashi5, Mariam AlSaeed1,4, Amal Almutairi1,4, Fatimah Alqubaishi1,4, Abdulellah Alturkistani3, Abdullah AlObaid3, Mohamed Abouelhoda4,5, Latifa AlMubarak1,4, Nada AlTassan4,5 and Malak Abedalthagafi1,5,*

1 Genomics Research Department, Saudi Human Genome Project, King Fahad Medical City and King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia

2 Montreal Neurological Institute, Montreal, Canada

3 Neurosurgery Department, King Fahad Medical City, Riyadh, Saudi Arabia

4 Saudi Human Genome Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia

5 Genetics Department, King Faisal Specialists Hospital and Research Center, Riyadh, Saudi Arabia

* These authors contributed equally to this work

Correspondence to:

Malak Abedalthagafi,email: [email protected]

Keywords: meningioma; FGFR3; NGS; genomics; CNS

Received: May 31, 2019     Accepted: August 12, 2019     Published: September 17, 2019

ABSTRACT

Background: With a prevalence of 170 000 adults in the US alone, meningiomas are the most common primary intracranial tumors. The management of skull base meningiomas is challenging due to their complexity and proximity to crucial nearby structures. The identification of oncogenic mutations has provided further insights into the tumorigenesis of meningioma and the possibility of targeted therapy.

This study aimed to further investigate the association of mutational profiles with anatomical distribution, histological subtype, WHO grade, and recurrence in patients with meningioma.

Methods: Tissue samples were collected from 71 patients diagnosed with meningioma from 2008 to 2016. A total of 51 cases were skull based. Samples were subjected to targeted sequencing using a next generation customized cancer gene panel (n = 66 genes analyzed).

Results: We detected genomic alterations (GAs) in 68 tumors, averaging 1.56 ± 1.07 genomic alterations (GAs) per sample. NF2 was the most frequently altered gene (36/71 cases). Interestingly, we identified a number of mutations in non-NF2 genes, including a hotspot TERTp c.−124: G > A mutation that may be related to poor prognosis and FGFR3 mutations that may represent biomarkers of a favorable prognosis as reported in other cancers.

Conclusions: We demonstrate that comprehensive genomic profiling in our population can reveal a potential new prognostic biomarkers of skull base meningioma. These mutations can enhance diagnostic accuracy and clinical decision-making. Among our findings were the identification of a TERTp mutation and the first report of FGFR3 mutations that may represent biomarkers for the identification of skull base meningioma patients with a favorable prognosis.


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