Distinct germ line polymorphisms underlie glioma morphologic heterogeneity

Area of Science:

• Genetics
• Neuro-oncology
• Molecular Epidemiology

Background:

• Genome-wide association studies (GWAS) identified single nucleotide polymorphisms (SNPs) near TERT, CCDC26, CDKN2A/B, PHLDB1, and RTEL1 associated with infiltrating glioma.
• It remained unclear if these SNP associations were general to glioma or specific to certain grades or subtypes.

Purpose of the Study:

• To investigate the association between specific susceptibility loci and glioma subtypes.
• To determine if germline polymorphisms predispose to distinct glioma morphologic subtypes.

Main Methods:

• Genotyped two case-control groups encompassing the spectrum of infiltrating glioma subtypes.
• Stratified analyses by glioma type to identify subtype-specific SNP associations.

Main Results:

• Germline polymorphisms are associated with different glioma subtypes.
• CCDC26 (8q24) polymorphisms strongly associate with oligodendroglial tumors (rs4295627, OR=2.05), but not glioblastoma.
• RTEL1 (20q13) polymorphisms associate with glioblastoma (rs2297440, OR=0.56), but not oligodendroglial tumors.
• CCDC26 SNPs show the strongest association with oligodendroglial tumors having combined 1p and 19q deletion (rs4295627, OR=2.77).

Conclusions:

• Specific SNPs are differentially associated with glioma subtypes, suggesting distinct genetic predispositions.
• These findings support hypotheses regarding the mechanisms of SNP involvement in glioma development.
• The results highlight the importance of considering tumor subtype in genetic association studies of glioma.