Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes

Journal: Nature

Published: 2018-01-24

DOI: 10.1038/nature25459

Affiliations: 17

Authors: 50

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Research Highlight

Gene duplications behind tumour aggressiveness



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 is activated in around 90% of cases of human pancreatic cancer.

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 been inactivated in the tumours.

The findings point towards a basic organizing principle behind pancreatic cancer — one that could be exploited for therapeutic purposes.

“We have introduced oncogenic dosage increase as a fundamentally important process,” TUM senior study author Roland Rad told Nature Reviews Gastroenterology & Hepatology.

Supported content

  1. Nature 554, 62–68 (2018). doi: 10.1038/nature25459
Institutions Share
TUM University Hospital Klinikum rechts der Isar (MRI), Germany 0.48
Wellcome Sanger Institute, United Kingdom (UK) 0.22
German Consortium of Translational Cancer Research (DKTK), Germany 0.08
Ludwig Maximilians University of Munich (LMU), Germany 0.06
Helmholtz Zentrum München - German Research Center for Environmental Health (HMGU), Germany 0.04
University of Oviedo (UniOvi), Spain 0.03
University of Cambridge, United Kingdom (UK) 0.02
University Hospital of Munich (KUM), LMU, Germany 0.02
Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), Spain 0.02
Asturias Central University Hospital (HUCA), Spain 0.02
Institute of Molecular and Oncological Medicine of Asturias (IMOMA), Spain 0.02
Nanomaterials and Nanotechnology Research Center (CINN), Spain 0.01