Germline POT1 Deregulation Can Predispose to Myeloid Malignancies in Childhood.

ABSTRACT: While the shelterin complex guards and coordinates the mechanism of telomere regulation, deregulation of this process is tightly linked to malignant transformation and cancer. Here, we present the novel finding of a germline stop-gain variant (p.Q199*) in the shelterin complex gene POT1, which was identified in a child with acute myeloid leukemia. We show that the cells overexpressing the mutated POT1 display increased DNA damage and chromosomal instabilities compared to the wildtype counterpart. Protein and mRNA expression analyses in the primary patient cells further confirm that, physiologically, the variant leads to a nonfunctional POT1 allele in the patient. Subsequent telomere length measurements in the primary cells carrying heterozygous POT1 p.Q199* as w

SUBMITTER: Michler P 

PROVIDER: S-EPMC8583981 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature