In-frame germline TP53 variant impairs p53 oligomerization and predisposes to cancer.

ABSTRACT: Germline loss-of-function variants in TP53 cause Li-Fraumeni syndrome (LFS) characterized by an early onset of various cancer types including sarcomas, adrenocortical carcinoma, and breast cancer. The most common are mutations in the DNA binding domain of p53, but alterations in the oligomerization domain also cause LFS with variable level of penetrance. Here we report identification of a novel germline in-frame deletion TP53 variant c.1015_1023del p.(E339_F341del) in a family with early-onset breast cancer and other malignancies. Using functional testing, we found that a short deletion in the oligomerization domain in the p.E339_F341del variant severely impaired transcriptional activity of p53 in human cells and in a yeast model. The loss of the transactivation activity was consistent wit

SUBMITTER: Vanikova L 

PROVIDER: S-EPMC12365031 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature