Inferring modes of evolution from colorectal cancer with residual polyp of origin

Oncotarget
Minsoo KimLisa Boardman

Abstract

Besides the classical evolutionary model of colorectal cancer (CRC) defined by the stepwise accumulation of mutations in which normal epithelium transforms through an intermediary polyp stage to cancer, a few studies have proposed alternative modes of evolution (MOE): early eruptive subclonal expansion, branching of the subclones in parallel evolution, and neutral evolution. However, frequencies of MOEs and their connection to mutational characteristics of cancer remain elusive. In this study, we analyzed patterns of somatic single nucleotide variations (SNVs) and copy number aberrations (CNAs) in CRC with residual polyp of origin from 13 patients in order to determine this relationship. For each MOE we defined an expected pattern with characteristic features of allele frequency distributions for SNVs in cancers and their matching adenomas. From these distinct patterns, we then assigned an MOE to each CRC case and found that stepwise progression was the most common (70% of cases). We found that CRC with the same MOE may exhibit different mutational spectra, suggesting that different mutational mechanisms can result in the same MOE. Inversely, cancers with different MOEs can have the same mutational spectrum, suggesting that the...Continue Reading

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Methods Mentioned

BETA
deamination
chromosomal aberration
exome sequencing
single cell sequencing

Software Mentioned

MOE
CNVnator
SIFT
Picard Tools
PolyPhen2
SomaticSniper
Database for Annotation Visualization and Integrated Discovery...
VarScan
ggplot2
Strelka

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