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

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 immunodefi

SUBMITTER: Schratz KE 

PROVIDER: S-EPMC10188244 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature