title: Genetic determinants at the interface of cancer and neurodegenerative disease.
abstract: It has been hypothesized that oncogenesis and neurodegeneration may share common mechanistic foundations. Recent evidence now reveals a number of genes in which alteration leads to either carcinogenesis or neurodegeneration, depending on cellular context. Pathways that have emerged as having critical roles in both cancer and neurodegenerative disease include those involving genes such as PARK2, ATM, PTEN, PTPRD, and mTOR. A number of mechanisms have been implicated, and commonly affected cellular processes include cell cycle regulation, DNA repair, and response to oxidative stress. For example, we have recently shown that the E3 ubiquitin ligase PARK2 is mutated or deleted in many different human malignancies and helps drive loss on chromosome 6q25.2-27, a genomic region frequently deleted in cancers. Mutation in PARK2 is also the most common cause of juvenile Parkinson's disease. Mutations in PARK2 result in an upregulation of its substrate cyclin E, resulting in dysregulated entry into the cell cycle. In neurons, this process results in cell death, but in cycling cells, the result is a growth advantage. Thus, depending on whether the cell affected is a dividing cell or a post-mitotic neuron, responses to these alterations may differ, ultimately leading to varying disease phenotypes. Here, we review the substantial data implicating specific genes in both cancer and neurodegenerative disease.
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: L G T
authors.initials: LG
authors.lastname: Morris
authors.forename: S
authors.initials: S
authors.lastname: Veeriah
authors.forename: T A
authors.initials: TA
authors.lastname: Chan
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology