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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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Viswanath P,Batsios G,Mukherjee J,Gillespie AM,Larson PEZ,Luchman HA,Phillips JJ,Costello JF,Pieper RO,Ronen SM

doi

10.1038/s41467-020-20312-y

subject

Has Abstract

pub_date

2021-01-04 00:00:00

pages

92

issue

1

issn

2041-1723

pii

10.1038/s41467-020-20312-y

journal_volume

12

pub_type

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