A recurrent mutation in PARK2 is associated with familial lung cancer

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

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)301-308
Number of pages8
JournalAmerican journal of human genetics
Issue number2
StatePublished - Feb 5 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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