Inferring modes of evolution from colorectal cancer with residual polyp of origin
Metrics: PDF 602 views | HTML 1306 views | ?
Minsoo Kim1,2, Brooke R. Druliner3, Nikolaos Vasmatzis2, Taejeong Bae2, Nicholas Chia2, Alexej Abyzov1,2 and Lisa A. Boardman3
1Program in Bioinformatics and Computational Biology, University of Minnesota, Minneapolis, MN 55455, USA
2Department of Health Sciences Research, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA
3Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA
Lisa A. Boardman, email: Boardman.Lisa@mayo.edu
Alexej Abyzov, email: Abyzov.Alexej@mayo.edu
Keywords: colorectal cancer; adenomatous polyp; cancer evolution; carcinogenesis; mutation
Received: July 12, 2017 Accepted: December 20, 2017 Published: December 26, 2017
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 same mutational mechanism can lead to different MOEs. The types of somatic substitutions, distribution of CNAs across genome, and mutated pathways did not correlate with MOEs. As this could be due to small sample size, these relations warrant further investigation. Our study paves the way to connect MOE with clinical and mutational characteristics not only in CRC but also to neoplastic transformation in other cancers.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.