Duke University

Bill H Diplas

Hai Yan

Darell D Bigner

Rui Yang

Landon Hansen

Yiping He

The majority of glioblastomas can be classified into molecular subgroups based on mutations in the TERT promoter (TERTp) and isocitrate dehydrogenase 1 or 2 (IDH). These molecular subgroups utilize distinct genetic mechanisms of telomere maintenance, either TERTp mutation leading to telomerase activation or ATRX-mutation leading to an alternative lengthening of telomeres phenotype (ALT). However, about 20% of glioblastomas lack alterations in TERTp and IDH. These tumors, designated TERTp-IDHglioblastomas, did not have well-established genetic biomarkers or defined mechanisms of telomere maintenance. The genetic landscape of TERTp-IDHglioblastoma includes tumors that have chromosomal rearrangements upstream of TERT. These rearrangements define a novel molecular subgroup of glioblastoma, that is a telomerase-positive subgroup driven by TERT-structural rearrangements (IDH-TERT).

Directing treatments for glioblastoma based on identifying a somatic structural rearrangement upstream from TERT gene

Methods that rapidly, sensitively, and specifically detect mutations in IDH1/2 and the TERT promoter employ amplification of particular portions of the genes that experience frequent and exquisitely localized mutations. The ability to distinguish between sequences that differ only by one nucleotide and which may be present in very low ratios is essential for such an assay.

Growing community of inventors

Durham, NC, United States of America

Bill H Diplas