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Non-invasive assessment of telomere maintenance mechanisms in brain tumors

Author

Listed:
  • Pavithra Viswanath

    (University of California San Francisco)

  • Georgios Batsios

    (University of California San Francisco)

  • Joydeep Mukherjee

    (University of California San Francisco)

  • Anne Marie Gillespie

    (University of California San Francisco)

  • Peder E. Z. Larson

    (University of California San Francisco)

  • H. Artee Luchman

    (University of Calgary)

  • Joanna J. Phillips

    (University of California San Francisco)

  • Joseph F. Costello

    (University of California San Francisco)

  • Russell O. Pieper

    (University of California San Francisco)

  • Sabrina M. Ronen

    (University of California San Francisco)

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.

Suggested Citation

  • Pavithra Viswanath & Georgios Batsios & Joydeep Mukherjee & Anne Marie Gillespie & Peder E. Z. Larson & H. Artee Luchman & Joanna J. Phillips & Joseph F. Costello & Russell O. Pieper & Sabrina M. Rone, 2021. "Non-invasive assessment of telomere maintenance mechanisms in brain tumors," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20312-y
    DOI: 10.1038/s41467-020-20312-y
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    Cited by:

    1. Francesc Muyas & Manuel José Gómez Rodriguez & Rita Cascão & Angela Afonso & Carolin M. Sauer & Claudia C. Faria & Isidro Cortés-Ciriano & Ignacio Flores, 2024. "The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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