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Review
. 2025 Jan;206(1):69-73.
doi: 10.1111/bjh.19851. Epub 2024 Oct 27.

Different phenotypes with different endings-Telomere biology disorders and cancer predisposition with long telomeres

Sharon A Savage  1 , Alison A Bertuch  2 ; Team Telomere and the Clinical Care Consortium for Telomere‐Associated Ailments (CCCTAA)
Collaborators, Affiliations
Review

Different phenotypes with different endings-Telomere biology disorders and cancer predisposition with long telomeres

Sharon A Savage et al. Br J Haematol. 2025 Jan.

Abstract

Rare germline pathogenic variants (GPVs) in genes essential in telomere length maintenance and function have been implicated in two broad classes of human disease. The telomere biology disorders (TBDs) are a spectrum of life-threatening conditions, including bone marrow failure, liver and lung disease, cancer and other complications caused by GPVs in telomere maintenance genes that result in short and/or dysfunctional telomeres and reduced cellular replicative capacity. In contrast, cancer predisposition with long telomeres (CPLT) is a disorder associated with elevated risk of a variety of cancers, primarily melanoma, thyroid cancer, sarcoma, glioma and lymphoproliferative neoplasms caused by GPVs in shelterin complex genes that lead to excessive telomere elongation and increased cellular replicative capacity. While telomeres are at the root of both disorders, the term TBD is used to convey the clinical phenotypes driven by critically short or otherwise dysfunctional telomeres and their biological consequences.

Keywords: cancer; genetics; telomere.

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Conflict of interest statement

Team Telomere, Inc., is a non‐profit family and patient support and advocacy organization. The CCCTAA is an international consortium of researchers and clinicians who collaborate to answer critical questions in the TBDs. Dr. Geraldine Aubert is employed by Repeat Diagnostics, a clinical laboratory specializing in telomere length measurement services. Drs. Alison Bertuch, Cristen Ebens and Kasiani Myers are consultants for a clinical trial sponsored by Elixirgen Therapeutics. Dr. Maria Molina‐Molina has received funds from Boehringer Ingelheim, Ferrer and Roche for providing scientific advice unrelated to this work.

References

    1. Heiss NS, Knight SW, Vulliamy TJ, Klauck SM, Wiemann S, Mason PJ, et al. X‐linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nat Genet. 1998;19(1):32–38. - PubMed
    1. Mitchell JR, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature. 1999;402(6761):551–555. - PubMed
    1. Vulliamy TJ, Marrone A, Knight SW, Walne A, Mason PJ, Dokal I. Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood. 2006;107(7):2680–2685. - PubMed
    1. Tummala H, Walne A, Dokal I. The biology and management of dyskeratosis congenita and related disorders of telomeres. Expert Rev Hematol. 2022;15:1–12. - PubMed
    1. Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after fifteen years of follow‐up. Haematologica. 2018;103(1):30–39. - PMC - PubMed