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T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to squamous cancers. | LitMetric

AI Article Synopsis

  • Patients with short telomere syndromes (STS) have an increased risk of developing certain solid cancers, specifically squamous cell carcinomas in the head and neck, anus, or skin, resembling cancer patterns in those with immunodeficiency.
  • Whole-genome sequencing revealed no significant chromosome instability in STS-associated cancers, but these cancers exhibited alterations that help maintain telomeres, like mutations in the TERT promoter.
  • A study on the immune status of STS patients showed significant T cell immunodeficiency at cancer diagnosis, suggesting that this immune deficiency, rather than changes in the cancer cells themselves, is responsible for the increased cancer risk in STS patients.

Article Abstract

Patients with short telomere syndromes (STS) are predisposed to developing cancer, believed to stem from chromosome instability in neoplastic cells. We tested this hypothesis in a large cohort assembled over the last 20 years. We found that the only solid cancers to which patients with STS are predisposed are squamous cell carcinomas of the head and neck, anus, or skin, a spectrum reminiscent of cancers seen in patients with immunodeficiency. Whole-genome sequencing showed no increase in chromosome instability, such as translocations or chromothripsis. Moreover, STS-associated cancers acquired telomere maintenance mechanisms, including telomerase reverse transcriptase (TERT) promoter mutations. A detailed study of the immune status of patients with STS revealed a striking T cell immunodeficiency at the time of cancer diagnosis. A similar immunodeficiency that impaired tumor surveillance was documented in mice with short telomeres. We conclude that STS patients’ predisposition to solid cancers is due to T cell exhaustion rather than autonomous defects in the neoplastic cells themselves.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188244PMC
http://dx.doi.org/10.1016/j.ccell.2023.03.005DOI Listing

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