Integrating Contemporary Biospecimens and Immunomethylomics into the study of the Glioma Genetics and Immunity - CIDR
Gliomas account for 80% of all malignant brain tumors and have an extremely poor prognosis, with a 5-year survival of 5.1%. The etiology of glioma remains poorly understood, with few established modifiable risk factors. Multiple studies have implicated infections in the development of glioma; however, the underlying mechanisms and putative causal pathogens remain unclear. In addition to risk, we have recently shown that reactivity to varicella zoster virus is also associated with a significant survival benefit in patients with glioma. Previous epidemiologic studies have investigated a limited number of pathogens using serological assays that only allowed detection. Recent analyses from our group have also highlighted that glioma subtypes have varying immune cells at diagnosis, and that there may be prognostic value.
This CIDR proposal has two parts to add to the parent R01- Discovering Infection-mediated Pathways of Glioma Etiology and Prognosis by Leveraging Multiplex Serology and Immunogenomics (R01 CA266676) that applies multiplex serology and targeted HLA sequencing to understand the interplay between germline genetics, antigen reactivity and glioma risk/survival.
- In the first part of this application, we seek to expand our current plans to include 447 Immune Profiles Study subjects that have contemporary treatment, and highly detailed longitudinal biospecimens and clinical data measured at every clinic visit across the course of treatment. We plan to genotype these subjects for inclusion in viral antigen measurement and HLA sequencing. We will also include 30 cross-study replicate samples from the UCSF Adult Glioma Study (dbGaP Study Accession: phs001497) in this genotyping project.
- The second part of this CIDR proposal seeks to analyze whole blood methylation to deconvolute blood cell proportions for 1592 glioma cases and 1147 matched controls from the Adult Glioma Study that do not have existing blood methylation. The derived blood cell proportions will facilitate a deeper understand of the subtype specific risk and prognosis associated with immune cell traits, integrate mediation by germline genetics, and hone the antigen associations by controlling for antigen presenting cells.
This proposal will unite two parallel, but independent and complementary studies, and will complete the viral, immunologic and genetic understanding of the association with viral reactivity and immune cells that will pave the way for functional studies. This will allow us to develop comprehensive immunogenomic models for predicting glioma risk and survival. Taken together, the proposed study will contribute new, high-quality data that will significantly advance our understanding of glioma pathogenesis, as well as inform avenues for prevention and improvement of outcomes in glioma patients.
- Type: Case Set
- Archive: The database of Genotypes and Phenotypes (dbGaP)