AJHG：帕金森的致病基因突变或与肺癌风险直接相关

  近日，来自威斯康星医学院的研究人员发现，一种帕金森致病基因或和和肺癌发病直接相关，相关研究发表于国际杂志American Journal of Human Genetics上。

  文章中研究者表示，通过进行全外显子组测序，我们鉴别出了一种名为PARK2的基因突变，其和早期帕金森疾病发病相关，而研究结果也发现该基因突变和家族性肺癌的发病存在一定关联。

  研究人员对一个家族多个患肺癌的个体进行外显子组测序，随后研究PARK2基因的功能，Donghai Xiong教授说道，特殊的遗传突变在一般人群中非常罕见，但本研究发现，PARK2基因的突变和家族性多个个体发生肺癌直接相关。

  本文的研究结果显示，和帕金森疾病发病相关的特殊遗传突变或许是引发肺癌的遗传易感因子，其也为研究人员进行后期更为深入的研究来揭示该基因的功能以及开发有效性的靶向性疗法提供一定的帮助。最后研究者Ming You说道，本研究为我们带来了意想不到的结果，我们的研究发现或许揭示了相同基因突变可以引发不同的疾病，也为后期治疗PARK2突变的肺癌患者带来希望。（转化医学网360zhyx.com）
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转化医学网推荐的原文阅读：

A Recurrent Mutation in PARK2 Is Associated with Familial Lung Cancer.
The American Journal of Human Genetics DOI: 10.1016/j.ajhg.2014.12.016
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.
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.