Characterization of genetic subclonal evolution in pancreatic cancer mouse models Journal Article

   

Authors:	Niknafs, N.; Zhong, Y.; Moral, J. A.; Zhang, L.; Shao, M. X.; Lo, A.; Makohon-Moore, A.; Iacobuzio-Donahue, C. A.; Karchin, R.
Article Title:	Characterization of genetic subclonal evolution in pancreatic cancer mouse models
Abstract:	The KPC mouse model, driven by the Kras and Trp53 transgenes, is well regarded for faithful recapitulation of human pancreatic cancer biology. However, the extent that this model recapitulates the subclonal evolution of this tumor type is unknown. Here we report evidence of continuing subclonal evolution after tumor initiation that largely reflect copy number alterations that target cellular processes of established significance in human pancreatic cancer. The evolutionary trajectories of the mouse tumors show both linear and branching patterns as well as clonal mixing. We propose the KPC model and derivatives have unexplored utility as a functional system to model the mechanisms and modifiers of tumor evolution. © 2019, The Author(s).
Keywords:	gene mutation; single nucleotide polymorphism; somatic mutation; missense mutation; nonhuman; pancreas cancer; genetic analysis; quality control; animal cell; mouse; animal tissue; biology; animal model; protein; genotype; gene frequency; histology; mathematical model; transgene; tumor growth; tumor; dna extraction; model; phylogeny; clone; copy number variation; germline mutation; clonal evolution; cancer; article; whole exome sequencing
Journal Title:	Nature Communications
Volume:	10
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2019-11-28
Start Page:	5435
Language:	English
DOI:	10.1038/s41467-019-13100-w
PUBMED:	31780749
PROVIDER:	scopus
PMCID:	PMC6882784
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85075750910&doi=10.1038%2fs41467-019-13100-w&partnerID=40&md5=b61e0b445f6403a8c970c9ea5119a385
Notes:	Article -- Source: Scopus

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