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Article

Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism

by 1,2 and 1,3,4,5,6,*
1
Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul 03722, Korea
2
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 03722, Korea
3
Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea
4
Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea
5
Department of Biochemistry & Molecular Biology, Yonsei University College of Medicine, Seoul 03722, Korea
6
Department of Research & Development, VeraVerse Inc., Seoul 03722, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Erica Salvati
Int. J. Mol. Sci. 2021, 22(20), 11101; https://doi.org/10.3390/ijms222011101
Received: 30 August 2021 / Revised: 4 October 2021 / Accepted: 13 October 2021 / Published: 14 October 2021
(This article belongs to the Special Issue Telomeres, Telomerase and Cancer)
Understanding the telomere maintenance mechanism (TMM) in immortal cancer cells is vital for TMM-targeted therapies in clinical settings. In this study, we classified four telomere maintenance mechanisms into telomerase, ALT, telomerase + ALT, and non-defined telomere maintenance mechanism (NDTMM) across 31 cancer types using 10,704 transcriptomic datasets from The Cancer Genome Atlas. Our results demonstrated that approximately 50% of the total cohort displayed ALT activity with high telomerase activity in most cancer types. We confirmed significant patient prognoses according to distinct TMMs in six cancer types: adrenocortical carcinoma (ACC), PAAD, HNSC, SARC, GBM, and metastatic cancer. Patients with metastasis had a poor prognosis in the ALT group (p < 0.006) subjected to RAS protein signal transduction. Glioblastoma patients had poor prognosis in NDTMM (p < 0.0043) and showed high levels of myeloid leukocyte activation. Pancreatic adenocarcinoma (p < 0.04) and head and neck squamous cell carcinoma (p < 0.046) patients had a good prognosis in the ALT group with high immune cell activation. Furthermore, we showed that master transcriptional regulators might affect the selection of the TMM pathway and explained why different telomere maintenance mechanisms exist. Furthermore, they can be used to segregate patients and predict responders to different TMM-targeted therapeutics. View Full-Text
Keywords: telomere maintenance mechanism; non-defined telomere maintenance mechanism; alternative lengthening of telomere telomere maintenance mechanism; non-defined telomere maintenance mechanism; alternative lengthening of telomere
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MDPI and ACS Style

Sung, J.-Y.; Cheong, J.-H. Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism. Int. J. Mol. Sci. 2021, 22, 11101. https://doi.org/10.3390/ijms222011101

AMA Style

Sung J-Y, Cheong J-H. Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism. International Journal of Molecular Sciences. 2021; 22(20):11101. https://doi.org/10.3390/ijms222011101

Chicago/Turabian Style

Sung, Ji-Yong, and Jae-Ho Cheong. 2021. "Pan-Cancer Analysis of Clinical Relevance via Telomere Maintenance Mechanism" International Journal of Molecular Sciences 22, no. 20: 11101. https://doi.org/10.3390/ijms222011101

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