Evidence for age-related contributions of DNA damage and epigenetics in brain tumorigenesis.

Glioblastoma (GBM) is a highly malignant primary brain tumour displaying rapid cell proliferation and infiltration. GBM primarily occurs at older age; however, younger populations have also been affected. In GBM and other cancers, genetic and epigenetic alterations promote tumorigenesis causing increased cell proliferation and invasiveness. This investigation explored epigenetic events as contributing factors, especially in gliomas that arise in patients aged 40-60 years. Furthermore, DNA damage in tumours with respect to age was assessed. Archival fixed tissues from 88 cases of glioblastoma and adjacent non-malignant tissues were tested. Global methylation and DNA damage were measured using ELISA detection of 5-methyl cytosine and 8-hydroxy guanine, respectively. IDH mutations and CDKN2 promoter hypermethylation were analysed by pyrosequencing. Tumour tissue was hypomethylated compared with non-malignant tissue (P = .001), and there was a trend towards increased methylation with increasing age. There was a significant increase in DNA damage in patients older than forty years compared with those aged forty years or younger (P = .035). CDKN2 promoter methylation levels followed the age trends of global methylation in this patient group. Patients younger than 60 had more frequently mutated IDH (P = .004). Conclusions: The data support the potential of epigenetic factors in promoting tumorigenesis in younger patients, while increased DNA damage contributes to tumorigenesis in the older patients.

Comparison of Tissue Molecular Biomarker Testing Turnaround Times and Concordance Between Standard of Care and the Biocartis Idylla Platform in Patients With Colorectal Cancer.

OBJECTIVES: Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti-epidermal growth factor receptor therapy and BRAF testing for prognostic stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories. METHODS: Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods. RESULTS: There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain reaction (PCR) had an average testing turnaround time of 5.6 days, send-out PCR of 22.5 days, in-house Sanger sequencing of 14.7 days, send-out Sanger of 17.8 days, in-house next-generation sequencing (NGS) of 12.5 days, and send-out NGS of 20.0 days. Standard testing had an average turnaround time of 11 days. Idylla average time to results was 4.9 days with a range of 0.4 to 13.5 days. CONCLUSIONS: The described cartridge-based system offers rapid and reliable testing of clinically actionable mutation in colorectal cancer specimens directly from formalin-fixed, paraffin-embedded tissue sections. Its simplicity and ease of use compared with other molecular techniques make it suitable for routine clinical laboratory testing.