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A recurrent mutation in PARK2 is associated with familial lung cancer.
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.
Afiliación
  • Xiong D; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • Wang Y; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • Kupert E; Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • Simpson C; Computational and Statistical Genomics Branch, National Human Genome Research Institute, NIH, Baltimore, MD 20892, USA.
  • Pinney SM; Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
  • Gaba CR; College of Medicine, University of Toledo, Toledo, OH 43614, USA.
  • Mandal D; Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
  • Schwartz AG; Karmanos Cancer Institute, Detroit, MI 48201, USA.
  • Yang P; Mayo Clinic, Rochester, MN 55905, USA.
  • de Andrade M; Mayo Clinic, Rochester, MN 55905, USA.
  • Pikielny C; Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03755, USA.
  • Byun J; Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03755, USA.
  • Li Y; Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03755, USA.
  • Stambolian D; Department of Ophthalmology and Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Spitz MR; Baylor College of Medicine, Houston, TX 77030, USA.
  • Liu Y; Baylor College of Medicine, Houston, TX 77030, USA.
  • Amos CI; Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03755, USA.
  • Bailey-Wilson JE; Computational and Statistical Genomics Branch, National Human Genome Research Institute, NIH, Baltimore, MD 20892, USA.
  • Anderson M; Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • You M; Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: myou@mcw.edu.
Am J Hum Genet ; 96(2): 301-8, 2015 Feb 05.
Article en En | MEDLINE | ID: mdl-25640678
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Ubiquitina-Proteína Ligasas / Neoplasias Pulmonares Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Am J Hum Genet Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Ubiquitina-Proteína Ligasas / Neoplasias Pulmonares Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Am J Hum Genet Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos