Nature Communications (Jul 2021)
Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine
- Yasaman Barekatain,
- Jeffrey J. Ackroyd,
- Victoria C. Yan,
- Sunada Khadka,
- Lin Wang,
- Ko-Chien Chen,
- Anton H. Poral,
- Theresa Tran,
- Dimitra K. Georgiou,
- Kenisha Arthur,
- Yu-Hsi Lin,
- Nikunj Satani,
- Elliot S. Ballato,
- Eliot I. Behr,
- Ana C. deCarvalho,
- Roel G. W. Verhaak,
- John de Groot,
- Jason T. Huse,
- John M. Asara,
- Raghu Kalluri,
- Florian L. Muller
Affiliations
- Yasaman Barekatain
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Jeffrey J. Ackroyd
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Victoria C. Yan
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Sunada Khadka
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Lin Wang
- Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University
- Ko-Chien Chen
- Department of Cancer Biology, The University of Texas MD Anderson Cancer Center
- Anton H. Poral
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Theresa Tran
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Dimitra K. Georgiou
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Kenisha Arthur
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Yu-Hsi Lin
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Nikunj Satani
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Elliot S. Ballato
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Eliot I. Behr
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- Ana C. deCarvalho
- Department of Neurosurgery, Henry Ford Hospital
- Roel G. W. Verhaak
- The Jackson Laboratory for Genomic Medicine
- John de Groot
- Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center
- Jason T. Huse
- Department of Pathology, The University of Texas MD Anderson Cancer Center
- John M. Asara
- Department of Medicine, Harvard Medical School, and Division of Signal Transduction, Beth Israel Deaconess Medical Center
- Raghu Kalluri
- Department of Cancer Biology, The University of Texas MD Anderson Cancer Center
- Florian L. Muller
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center
- DOI
- https://doi.org/10.1038/s41467-021-24240-3
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 13
Abstract
The metabolite methylthioadenosine (MTA) inhibits PRMT5. Therefore, MTA accumulation due to MTA phosphorylase (MTAP) deletion has been proposed as a vulnerability for PRMT5-targeted therapy in cancer. Here, the authors show that MTA does not accumulate in MTAP-deficient cancer cells but is secreted and metabolized by MTAP-intact cells in the tumour microenvironment.
