Tumorigenesis in Parkinsonís Disease
Research Grant, 2014
Objective/Rationale: † † † † † ††
The aim of the study is to investigate whether disease-causing genetic mutations in Parkinsonís disease (PD), particularly in the LRRK2 gene, also predispose individuals to different types of cancer. A link between Parkinsonís disease and cancer is well described for several PD-associated genes, which may be either tumor-suppressor genes or tumor-causing genes. We propose a role for these mutations at the interface of rapid cell growth seen in cancer and cell death seen in Parkinsonís disease.†
We will study the role of mutations, especially in LRRK2, in the formation of cancer by sequencing stored tumor cells of patients who have both Parkinsonís disease and a history of cancer. We will perform comparative whole exome sequencing of tumor tissue and normal tissue (typically blood) in PD individuals, with emphasis on those with proven disease-causing mutations in order to compare the genes found in tumor tissue and normal tissue in the same individual. We will investigate the tumors of these individuals in great detail and map any mutations onto known biological pathways.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
This study has the potential to reveal causal mechanisms of neurodegeneration in Parkinsonís disease. If mutations in PD genes not only predispose to PD but also to specific mutations in certain cell types potentially leading to tumors, this will be of great relevance with respect to monitoring and early detection of cancer in these mutation carriers. Specifically, by unraveling novel LRRK2-associated signaling pathways, as well as overlapping pathways in PD and cancer, this study has the potential to open up complete novel strategies in targeting cell death in LRRK2-associated PD.
Anticipated Outcome: † † † † †
In addition to possibly shedding light on a disease pathway in Parkinsonís disease, our study has the potential to open up completely novel strategies in targeting cell death in genetic forms of Parkinsonís disease. In addition, findings may have implications for cancer treatment for these patients.
Group Leader at Hertie Institute for Clinical Brain Research
Co-founder at Center for Genomics and Transcriptomics GmbH
Location: Tuebingen, Germany
Associate Professor of Neurology at Albert Einstein College of Medicine
Attending Neurologist at Beth Israel Medical Center
Location: New York, New York, United States