Non-invasive assessment of telomere maintenance mechanisms in brain tumors
Abstract
Telomere maintenance is a universal hallmark of cancer. Most tumors including low-grade oligodendrogliomas use telomerase reverse transcriptase (TERT) expression for telomere maintenance while astrocytomas use the alternative lengthening of telomeres (ALT) pathway. Although TERT and ALT are hallmarks of tumor proliferation and attractive therapeutic targets, translational methods of imaging TERT and ALT are lacking. Here we show that TERT and ALT are associated with unique 1H-magnetic resonance spectroscopy (MRS)-detectable metabolic signatures in genetically-engineered and patient-derived glioma models and patient biopsies. Importantly, we have leveraged this information to mechanistically validate hyperpolarized [1-13C]-alanine flux to pyruvate as an imaging biomarker of ALT status and hyperpolarized [1-13C]-alanine flux to lactate as an imaging biomarker of TERT status in low-grade gliomas. Collectively, we have identified metabolic biomarkers of TERT and ALT status that provide a way of integrating critical oncogenic information into non-invasive imaging modalities that can improve tumor diagnosis and treatment response monitoring.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 04, 2021
- Source ID
- 10.1038/s41467-020-20312-y
Entities
People
- Anne Marie Gillespie
- Georgios Batsios
- H. Artee Luchman
- Joanna J Phillips
- Joseph F. Costello
- Joydeep Mukherjee
- Pavithra Viswanath
- Peder Larson
- Russell O. Pieper
- Sabrina M. Ronen
Organizations
- Office of Extramural Research
- United States Department of Defense
- United States Department of Health and Human Services