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Pan-Cancer Analysis of Alternative Lengthening of Telomere Activity

1
Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea
2
Department of Health Science and Technology, Samsung Advanced Institute of Health Science and Technology, Sungkyunkwan University, Seoul 06351, Korea
3
Division of Biomedical Informatics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
4
Department of Molecular Cell Biology, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(8), 2207; https://doi.org/10.3390/cancers12082207
Received: 30 June 2020 / Revised: 1 August 2020 / Accepted: 5 August 2020 / Published: 7 August 2020
Alternative lengthening of telomeres (ALT) is a telomerase-independent mechanism that extends telomeres in cancer cells. It influences tumorigenesis and patient survival. Despite the clinical significance of ALT in tumors, the manner in which ALT is activated and influences prognostic outcomes in distinct cancer types is unclear. In this work, we profiled distinct telomere maintenance mechanisms (TMMs) using 8953 transcriptomes of 31 different cancer types from The Cancer Genome Atlas (TCGA). Our results demonstrated that approximately 29% of cancer types display high ALT activity with low telomerase activity in the telomere-lengthening group. Among the distinct ALT mechanisms, homologous recombination was frequently observed in sarcoma, adrenocortical carcinoma, and kidney chromophobe. Five cancer types showed a significant difference in survival in the presence of high ALT activity. Sarcoma patients with elevated ALT had unfavorable risks (p < 0.038) coupled with a high expression of TOP2A, suggesting this as a potential drug target. On the contrary, glioblastoma patients had favorable risks (p < 0.02), and showed low levels of antigen-presenting cells. Together, our analyses highlight cancer type-dependent TMM activities and ALT-associated genes as potential therapeutic targets. View Full-Text
Keywords: telomere maintenance mechanism; alternative lengthening of telomeres; cancers; gene expression; survival analysis telomere maintenance mechanism; alternative lengthening of telomeres; cancers; gene expression; survival analysis
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MDPI and ACS Style

Sung, J.-Y.; Lim, H.-W.; Joung, J.-G.; Park, W.-Y. Pan-Cancer Analysis of Alternative Lengthening of Telomere Activity. Cancers 2020, 12, 2207. https://doi.org/10.3390/cancers12082207

AMA Style

Sung J-Y, Lim H-W, Joung J-G, Park W-Y. Pan-Cancer Analysis of Alternative Lengthening of Telomere Activity. Cancers. 2020; 12(8):2207. https://doi.org/10.3390/cancers12082207

Chicago/Turabian Style

Sung, Ji-Yong, Hee-Woong Lim, Je-Gun Joung, and Woong-Yang Park. 2020. "Pan-Cancer Analysis of Alternative Lengthening of Telomere Activity" Cancers 12, no. 8: 2207. https://doi.org/10.3390/cancers12082207

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