Rare POLN mutations confer risk for familial nasopharyngeal carcinoma through weakened Epstein-Barr virus lytic replication.

ABSTRACT:

Background

Nasopharyngeal carcinoma (NPC) exhibits significant familial aggregation; however, its susceptibility genes are largely unknown. Thus, this study aimed to identify germline mutations that might contribute to the risk of familial NPC, and explore their biological functions.

Methods

Whole-exome sequencing was performed in 13 NPC pedigrees with multiple cases. Mutations co-segregated with disease status were further validated in a cohort composed of 563 probands from independent families, 2,953 sporadic cases, and 3,175 healthy controls. Experimental studies were used to explore the functions of susceptibility genes and their disease-related mutations.

Findings

The three rare missense mutations in POLN (DNA polymerase nu) gene, P577L, R303Q, and F545C, were as

SUBMITTER: Xiao RW 

PROVIDER: S-EPMC9486052 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature