Genetic alterations in non-syndromic, familial gliomas in first degree relatives: A systematic review

Clin Neurol Neurosurg. 2020 Nov:198:106222. doi: 10.1016/j.clineuro.2020.106222. Epub 2020 Sep 10.

Abstract

Objective: Despite numerous reports in syndromic gliomas, the underlying genetic and molecular basis of familial, non-syndromic gliomas, in first degree relatives, remains unclear. This rare cohort of patients harboring invasive primary brain tumors with poor prognosis may provide a potential substrate of understanding the complex genetic cascade triggering tumorigenesis.

Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) 2015 and The Cochrane Handbook of Systematic Reviews of Interventions. PubMed/MEDLINE, Embase and CENTRAL databases were accessed with set inclusion and exclusion criteria.

Results: Following returns of 6756 articles, systematic analysis resulted in 48 papers, with 18 case series, 4 linkage analysis, 3 case-control studies, 1 cohort study, and 22 case reports. A total of 164 first degree relatives of 72 families were analyzed. The most common genetic alterations associated with non-syndromic familial gliomas reported to affect chromosomes 17 (51.1 % germline and 9.3 % tumor mutations), 22 (15.6 % germline and 6 % tumor mutations) and 1 and 19 (4.4 % germline and 9.3 % tumor mutations), with the most commonly affected genes TP53 (8.5 %) and NF2 (3.7 %). Tumor suppressors or cell-cycle regulators, cell signaling and transcription regulation or methylation were the most common gene function categories.

Conclusion: Four specific chromosomes (17, 22, 1 and 19) and two specific genes (TP53 and NF2) appear to be most commonly involved. This appears to be the first systematic review of genetic factors underlying non-syndromic glioma clustering in families. The defined list of genetic abnormalities, linked to familial gliomas, may facilitate therapeutic targets and future treatment design.

Keywords: Familial gliomas; Genetics; Non-syndromic gliomas; Tumorig; enesis.

Publication types

  • Case Reports
  • Review
  • Systematic Review

MeSH terms

  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics*
  • Case-Control Studies
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Cohort Studies
  • Glioma / diagnosis*
  • Glioma / genetics*
  • Humans
  • Mutation / genetics*
  • Pedigree