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Citations to this article

Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations
Lindley Maryoung, … , Richard C. Wang, Christine Kim Garcia
Lindley Maryoung, … , Richard C. Wang, Christine Kim Garcia
Published February 13, 2017
Citation Information: J Clin Invest. 2017;127(3):982-986. https://doi.org/10.1172/JCI91161.
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Brief Report Aging Pulmonology Article has an altmetric score of 8

Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations

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Abstract

Germline coding mutations in different telomere-related genes have been linked to autosomal-dominant familial pulmonary fibrosis. Individuals with these inherited mutations demonstrate incomplete penetrance of clinical phenotypes affecting the lung, blood, liver, skin, and other organs. Here, we describe the somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocytes of approximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-specific ribonuclease (PARN), another gene linked to telomerase function. While these promoter mutations were initially identified as oncogenic drivers of cancer, individuals expressing the mutations have no history of cancer. Neither promoter mutation was found in population-based cohorts of similar or advanced age. The TERT promoter mutations were found more frequently in cis with the WT allele than the TERT coding sequence mutation. EBV-transformed lymphoblastoid B cell lines (LCLs) derived from subjects with TERT promoter mutations showed increased telomerase expression and activity compared with cell lines from family members with identical coding mutations. TERT promoter mutations resulted in an increased proliferation of LCLs and demonstrated positive selection over time. The persistence and recurrence of noncoding gain-of-function mutations in these cases suggests that telomerase activation is not only safely tolerated but also advantageous for clonal expansion.

Authors

Lindley Maryoung, Yangbo Yue, Ashley Young, Chad A. Newton, Cindy Barba, Nicolai S.C. van Oers, Richard C. Wang, Christine Kim Garcia

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 Total
Citations: 3 5 6 9 6 6 4 5 44
Citation information
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Citations to this article in year 2020 (6)

Title and authors Publication Year
Merkel Cell Polyomavirus Small T Antigen Activates Noncanonical NF-κB Signaling to Promote Tumorigenesis
J Zhao, Y Jia, S Shen, J Kim, X Wang, E Lee, I Brownell, JH Cho-Vega, C Lewis, J Homsi, RR Sharma, RC Wang
Molecular cancer research : MCR 2020
Cancer spectrum and outcomes in the Mendelian short telomere syndromes
KE Schratz, L Haley, SK Danoff, AL Blackford, AE DeZern, CD Gocke, AS Duffield, M Armanios
Blood 2020
Cancer and myeloid clonal evolution in the short telomere syndromes
KE Schratz, M Armanios
Current Opinion in Genetics & Development 2020
Telomerase reverse transcriptase promoter mutations in thyroid carcinomas: implications in precision oncology—a narrative review
X Yuan, T Liu, D Xu
Annals of translational medicine 2020
Activating somatic and germline TERT promoter variants in myeloid malignancies
V Nofrini, C Matteucci, F Pellanera, P Gorello, DD Giacomo, AG Fernandez, C Nardelli, T Iannotti, L Brandimarte, S Arniani, M Moretti, A Gili, G Roti, VD Battista, S Colla, C Mecucci
Leukemia 2020
Clonal hematopoiesis in the inherited bone marrow failure syndromes
FD Tsai, RC Lindsley
Blood 2020

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