Skip Navigation

Publication Detail

Title: A recurrent mutation in PARK2 is associated with familial lung cancer.

Authors: Xiong, Donghai; Wang, Yian; Kupert, Elena; Simpson, Claire; Pinney, Susan M; Gaba, Colette R; Mandal, Diptasri; Schwartz, Ann G; Yang, Ping; de Andrade, Mariza; Pikielny, Claudio; Byun, Jinyoung; Li, Yafang; Stambolian, Dwight; Spitz, Margaret R; Liu, Yanhong; Amos, Christopher I; Bailey-Wilson, Joan E; Anderson, Marshall; You, Ming

Published In Am J Hum Genet, (2015 Feb 05)

Abstract: PARK2, a gene associated with Parkinson disease, is a tumor suppressor in human malignancies. Here, we show that c.823C>T (p.Arg275Trp), a germline mutation in PARK2, is present in a family with eight cases of lung cancer. The resulting amino acid change, p.Arg275Trp, is located in the highly conserved RING finger 1 domain of PARK2, which encodes an E3 ubiquitin ligase. Upon further analysis, the c.823C>T mutation was detected in three additional families affected by lung cancer. The effect size for PARK2 c.823C>T (odds ratio = 5.24) in white individuals was larger than those reported for variants from lung cancer genome-wide association studies. These data implicate this PARK2 germline mutation as a genetic susceptibility factor for lung cancer. Our results provide a rationale for further investigations of this specific mutation and gene for evaluation of the possibility of developing targeted therapies against lung cancer in individuals with PARK2 variants by compensating for the loss-of-function effect caused by the associated variation.

PubMed ID: 25640678 Exiting the NIEHS site

MeSH Terms: Base Sequence; DNA Primers/genetics; Exome/genetics; Female; Genetic Predisposition to Disease/genetics*; Germ-Line Mutation/genetics; Humans; Lung Neoplasms/genetics*; Male; Molecular Sequence Data; Mutation, Missense/genetics; Odds Ratio; Pedigree; Sequence Analysis, DNA; Ubiquitin-Protein Ligases/genetics*

Back
to Top
Last Reviewed: October 02, 2024