Multiple outcomes of the germline p16^INK4a mutation affecting senescence and immunity in human skin.

ABSTRACT: The integrated behaviour of multiple senescent cell types within a single human tissue leading to the development of malignancy is unclear. Patients with Familial Melanoma Syndrome (FMS) have heterozygous germline defects in the CDKN2A gene coding for the cyclin inhibitor p16^INK4a. Melanocytes within skin biopsies from FMS patients express significantly less p16^INK4a but express higher levels of the DNA-damage protein 𝛾H2AX a than fibroblastic cells. However, patient fibroblasts also exhibit defects since senescent cells do not increase in the skin during ageing and fibroblasts isolated from the skin of patients have increased replicative capacity compared to control fibroblasts in vitro, culminating in abnormal nuclear morphology. Patient derived fibroblasts also se

SUBMITTER: Subramanian P 

PROVIDER: S-EPMC11822638 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature