Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes
Duplications of cancer-associated gene mutations help explain the aggressiveness and early metastatic nature of pancreatic tumours, scientists from Technical University Munich (TUM) have found.
The researchers created cancer cell lines from 38 mice engineered to develop pancreatic tumors carrying a single mutant copy of KRAS, an oncogene that
They found that, in the early stages of tumour evolution, either the mutated KRAS gene itself became doubled or there was an oncogenic gain of some other cancer-linked mutation. Which cancer-promoting gene amplification occurred depended on which tumour suppressor genes had first
The findings point towards a basic organizing principle behind pancreatic cancer — one that could
“We have introduced oncogenic dosage increase as a
- Nature 554, 62–68 (2018). doi: 10.1038/nature25459