摘要 |
<p>There are currently few therapeutic options for patients with pancreatic cancers and new insights into the pathogenesis of this lethal disease are urgently needed. To this end, we performed a comprehensive analysis of the genes altered in 24 pancreatic tumors. First, we determined the sequences of 23,781 transcripts, representing 20,583 protein-encoding genes, in DNA from these tumors. Second, we searched for homozygous deletions and amplifications using microarrays querying˜one million single nucleotide polymorphisms in each sample. Third, we analyzed the transcriptomes of the same samples using SAGE and next-generation sequencing-by-synthesis technologies. We found that pancreatic cancers contain an average of 63 genetic alterations, of which 49 are point mutations, 8 are homozygous deletions, and 6 are amplifications. Further analyses revealed a core set of 12 regulatory processes or pathways that were each genetically altered in 70% to 100% of the samples. The data suggest that dysregulation of this core set of pathways is responsible for the major features of pancreatic tumorigenesis.</p> |
申请人 |
THE JOHNS HOPKINS UNIVERSITY |
发明人 |
VOGELSTEIN, BERT;KINZLER, KENNETH, W.;PARSONS, DONALD WILLIAM;JONES, SIAN;ZHANG, XIAOSONG;LIN, JIMMY CHANG-HO;LEARY, REBECCA J.;ANGENENDT, PHILIPP;PAPADOPOULOS, NICKOLAS;VELCULESCU, VICTOR;PARMIGIANI, GIOVANNI;KARCHIN, RACHEL;KERN, SCOTT;HRUBAN, RALPH;ESHLEMAN, JAMES R.;GOGGINS, MICHAEL;KLEIN, ALISON |