Correlation of genetic alterations by whole-exome sequencing with clinical outcomes of glioblastoma patients from the Lebanese population.

Autor: Saadeh FS; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America., Morsi RZ; Department of Neurology, University of Chicago, Chicago, Illinois, United States of America., El-Kurdi A; Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon., Nemer G; Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon., Mahfouz R; Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon., Charafeddine M; Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon., Khoury J; Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon., Najjar MW; Division of Neurosurgery, Department of Surgery, American University of Beirut Medical Center, Beirut, Lebanon., Khoueiry P; Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon., Assi HI; Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Nov 25; Vol. 15 (11), pp. e0242793. Date of Electronic Publication: 2020 Nov 25 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0242793
Abstrakt: Introduction: Glioblastoma (GBM) is an aggressive brain tumor associated with high degree of resistance to treatment. Given its heterogeneity, it is important to understand the molecular landscape of this tumor for the development of more effective therapies. Because of the different genetic profiles of patients with GBM, we sought to identify genetic variants in Lebanese patients with GBM (LEB-GBM) and compare our findings to those in the Cancer Genome Atlas (TCGA).
Methods: We performed whole exome sequencing (WES) to identify somatic variants in a cohort of 60 patient-derived GBM samples. We focused our analysis on 50 commonly mutated GBM candidate genes and compared mutation signatures between our population and publicly available GBM data from TCGA. We also cross-tabulated biological covariates to assess for associations with overall survival, time to recurrence and follow-up duration.
Results: We included 60 patient-derived GBM samples from 37 males and 23 females, with age ranging from 3 to 80 years (mean and median age at diagnosis were 51 and 56, respectively). Recurrent tumor formation was present in 94.8% of patients (n = 55/58). After filtering, we identified 360 somatic variants from 60 GBM patient samples. After filtering, we identified 360 somatic variants from 60 GBM patient samples. Most frequently mutated genes in our samples included ATRX, PCDHX11, PTEN, TP53, NF1, EGFR, PIK3CA, and SCN9A. Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). EGFR and NF1 mutations were associated with the frontal lobe and temporal lobe in our LEB-GBM cohort, respectively.
Conclusions: Our WES analysis confirmed the similarity in mutation signature of the LEB-GBM population with TCGA cohorts. It showed that 1 out of the 50 commonly GBM candidate gene mutations is associated with decreased overall survival among the Lebanese cohort. This study also highlights the need for studies with larger sample sizes to inform clinicians for better prognostication and management of Lebanese patients with GBM.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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