A recurrent mutation in PARK2 is associated with familial lung cancer. Am J Hum Genet 2015 Feb 05;96(2):301-8
Date
02/03/2015Pubmed ID
25640678Pubmed Central ID
PMC4320264DOI
10.1016/j.ajhg.2014.12.016Scopus ID
2-s2.0-84925106543 (requires institutional sign-in at Scopus site) 65 CitationsAbstract
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.
Author List
Xiong D, Wang Y, Kupert E, Simpson C, Pinney SM, Gaba CR, Mandal D, Schwartz AG, Yang P, de Andrade M, Pikielny C, Byun J, Li Y, Stambolian D, Spitz MR, Liu Y, Amos CI, Bailey-Wilson JE, Anderson M, You MMESH terms used to index this publication - Major topics in bold
Base SequenceDNA Primers
Exome
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Lung Neoplasms
Male
Molecular Sequence Data
Mutation, Missense
Odds Ratio
Pedigree
Sequence Analysis, DNA
Ubiquitin-Protein Ligases
