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Journal article
Parkinson disease (PARK) genes are somatically mutated in cutaneous melanoma
Neurology. Genetics, Vol.2(3), e70
Jun/2016
Abstract
OBJECTIVE: To assess whether Parkinson disease (PD) genes are somatically mutated in cutaneous melanoma (CM) tissue, because CM occurs in patients with PD at higher rates than in the general population and PD is more common than expected in CM cohorts.METHODS: We cross-referenced somatic mutations in metastatic CM detected by whole-exome sequencing with the 15 known PD (PARK) genes. We computed the empirical distribution of the sum of mutations in each gene (Smut) and of the number of tissue samples in which a given gene was mutated at least once (SSampl) for each of the analyzable genes, determined the 90th and 95th percentiles of the empirical distributions of these sums, and verified the location of PARK genes in these distributions. Identical analyses were applied to adenocarcinoma of lung (ADENOCA-LUNG) and squamous cell carcinoma of lung (SQUAMCA-LUNG). We also analyzed the distribution of the number of mutated PARK genes in CM samples vs the 2 lung cancers.RESULTS: Somatic CM mutation analysis (n = 246) detected 315,914 mutations in 18,758 genes. Somatic CM mutations were found in 14 of 15 PARK genes. Forty-eight percent of CM samples carried ?1 PARK mutation and 25% carried multiple PARK mutations. PARK8 mutations occurred above the 95th percentile of the empirical distribution for SMut and SSampl. Significantly more CM samples harbored multiple PARK gene mutations compared with SQUAMCA-LUNG (p = 0.0026) and with ADENOCA-LUNG (p <0.0001).CONCLUSIONS: The overrepresentation of somatic PARK mutations in CM suggests shared dysregulated pathways for CM and PD.
Details
- Title
- Parkinson disease (PARK) genes are somatically mutated in cutaneous melanoma
- Creators
- Rivka Inzelberg (null) - Tel Aviv Sourasky Medical CenterYardena Samuels (null) - 972WIS_INST___122Esther Azizi (null) - Tel Aviv UniversityNouar Qutob (null) - 972WIS_INST___122Lilah Inzelberg (null) - Tel Aviv UniversityEytan Domany (null) - 972WIS_INST___89Edna Schechtman (null) - Ben-Gurion University of the NegevEitan Friedman (null) - Sheba Medical Center
- Resource Type
- Journal article
- Publication Details
- Neurology. Genetics, Vol.2(3), e70; Jun/2016
- Number of pages
- 8
- Language
- English
- DOI
- https://doi.org/10.1212/NXG.0000000000000070
- Grant note
- Y. Samuels is supported by the Israel Science Foundation grants 1604/13 and 877/13, the ERC (StG-335377), the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics, the estate of Alice Schwarz-Gardos, the estate of John Hunter, the Knell Family, the Peter and Patricia Gruber Award, and the Hamburger Family. E. Domany is supported by a grant from the Leir Charitable Foundation. Rivka Inzelberg: drafting/revising the manuscript, study concept or design, analysis or interpretation of data. Yardena Samuels: drafting/revising the manuscript, study concept or design, analysis or interpretation of data, acquisition of data. Esther Azizi: drafting/revising the manuscript, study concept or design. Nouar Qutob: drafting/revising the manuscript, acquisition of data. Lilah Inzelberg: drafting/revising the manuscript, analysis or interpretation of data. Edna Schechtman: drafting/revising the manuscript, analysis or interpretation of data, statistical analysis. Eytan Domany: drafting/revising the manuscript, analysis or interpretation of data. Eitan Friedman: drafting/revising the manuscript, study concept or design, analysis or interpretation of data.
- Record Identifier
- 993264661703596
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