TY - JOUR
T1 - A recurrent mutation in PARK2 is associated with familial lung cancer
AU - Xiong, Donghai
AU - Wang, Yian
AU - Kupert, Elena
AU - Simpson, Claire
AU - Pinney, Susan M.
AU - Gaba, Colette R.
AU - Mandal, Diptasri
AU - Schwartz, Ann G.
AU - Yang, Ping
AU - De Andrade, Mariza
AU - Pikielny, Claudio
AU - Byun, Jinyoung
AU - Li, Yafang
AU - Stambolian, Dwight
AU - Spitz, Margaret R.
AU - Liu, Yanhong
AU - Amos, Christopher I.
AU - Bailey-Wilson, Joan E.
AU - Anderson, Marshall
AU - You, Ming
N1 - Funding Information:
This work was supported in part by grants and contracts from the NIH (R01CA134433, R01CA134682, R01CA113793, R01CA129533, U01CA76293, P30-ES006096, RO1CA127219, N01-HG-65404, U19CA148127, P30CA023108, K07CA181480, and HHSN268201200007C), the Intramural Research Program of the NIH National Human Genome Research Institute, and the Advancing a Healthier Wisconsin fund. C.S. is supported in part by the National Lung Cancer Partnership, Free to Breathe, and the Lung Cancer Initiative of North Carolina.
Publisher Copyright:
© 2015 The American Society of Human Genetics.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2015/2/5
Y1 - 2015/2/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84925106543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925106543&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2014.12.016
DO - 10.1016/j.ajhg.2014.12.016
M3 - Article
C2 - 25640678
AN - SCOPUS:84925106543
VL - 96
SP - 301
EP - 308
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 2
ER -