Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignancies
摘要：
Mutation of the gene , which encodes an E3 ligase, is the most common cause of early-onset . In a search for multisite suppressors, we identified as a frequently targeted gene on 6q25.2-q27 in . Here we describe inactivating somatic mutations and frequent intragenic deletions of in . The mutations in occur in the same domains, and sometimes at the same residues, as the germline mutations causing familial . -specific mutations abrogate the growth-suppressive effects of the protein. mutations in decrease 's E3 , compromising its ability to ubiquitinate E and resulting in mitotic instability. These data strongly point to as a suppressor on 6q25.2-q27. Thus, , a gene that causes neuronal dysfunction when mutated in the germline, may instead contribute to when altered in non-neuronal somatic cells.
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关键词：
Animals Humans Mice Glioblastoma Colonic Neoplasms Lung Neoplasms Neoplasms, Experimental Parkinson Disease Ubiquitin-Protein Ligases DNA Mutational Analysis
DOI：
10.1038/ng.491
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年份：
2010
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