PO-339 Intratumour heterogeneity in a pancreatic cancer mouse model

Abstract

IntroductionIntratumour heterogeneity has been observed in multiple cancers and has been postulated as a critical aspect for tumour metastasis and treatment resistance. Therefore, a further characterisation of its role in cancer progression and metastasis has become essential. Pancreatic cancer in humans has a dismal prognosis with only 8% of patients surviving more than 5 years after diagnosis. Mouse models of pancreatic cancer, based on the expression of an oncogenic version of Kras in the pancreas, have been widely used to study the molecular pathways involved in pancreatic cancer progression, nevertheless there is still controversy about their utility to study the genetic complexity observed in the human tumours.Material and methodsWe have performed multi-sampling exome and genome sequencing in primary and metastatic lesions, as well as in primary cell cultures generated in an oncogenic Kras-mediated mouse model of pancreatic cancer.Results and discussionsWe have observed that murine tumours recapitulate the genetic complexity observed in the human tumours like a monofocal origin of the aggressive disease, multi-clonal intratumour heterogeneity with clone convergent evolution, independent waves of metastatic colonisation and the presence of chromotripsis.ConclusionOur results show that the oncogenic Kras-based mouse model is a very good tool for the study of the dynamics of intratumour heterogeneity and that it also reflects faithfully the genomic processes observed in human pancreatic tumours. Consequently, we propose that a deeper genomic study of these murine tumours could provide a better understanding of the role of intratumour heterogeneity in tumour progression and metastasis.