An annual estimate of ~200,000 patients inflicted by pancreatic cancer with a mortality rate of ~100% makes this specific type of cancer quite a challenge. The authors use almost all of the modern techniques available to them to detail the cellular state of this cancer type. They sequenced the coding genome of 24 patients and identified 1562 somatic mutations (25.5% synonymous, 62.4% missense, 3.8% nonsense, 5.0% small indels,
and 3.3% splice sites or within UTRs). Of the 20,661 genes analyzed by sequencing, 1327 had at least one mutation, and 148 had two or more mutations. The authors then structurally modelled 404 of the missense mutations, where 55 of them were close to an important interface and likely to affect protein function. In general, the average number of mutations in these tumors (77) are considerably lower than that of say breast cancer (101), possibly denoting fewer generations after tumorigensis.
Then, using SNP arrays the authors mapped genetic deletions or amplifications. Then they combined these data plus mutations plus gene-expression profiles to find key proteins in the emergence of this tumor. These analyses identified 69 gene sets that were genetically altered in the majority of the 24 cancers examined. 31 of these sets could be further grouped into 12 core signaling pathways including KRAS and TGF-b.
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