Spatial mutation patterns as markers of early colorectal tumor cell mobility

Proceedings of the National Academy of Sciences of the United States of America
Marc D RyserD Shibata

Abstract

A growing body of evidence suggests that a subset of human cancers grows as single clonal expansions. In such a nearly neutral evolution scenario, it is possible to infer the early ancestral tree of a full-grown tumor. We hypothesized that early tree reconstruction can provide insights into the mobility phenotypes of tumor cells during their first few cell divisions. We explored this hypothesis by means of a computational multiscale model of tumor expansion incorporating the glandular structure of colorectal tumors. After calibrating the model to multiregional and single gland data from 19 human colorectal tumors using approximate Bayesian computation, we examined the role of early tumor cell mobility in shaping the private mutation patterns of the final tumor. The simulations showed that early cell mixing in the first tumor gland can result in side-variegated patterns where the same private mutations could be detected on opposite tumor sides. In contrast, absence of early mixing led to nonvariegated, sectional mutation patterns. These results suggest that the patterns of detectable private mutations in colorectal tumors may be a marker of early cell movement and hence the invasive and metastatic potential of the tumor at the s...Continue Reading

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Citations

Oct 8, 2019·Journal of the National Comprehensive Cancer Network : JNCCN·Rona Yaeger
Mar 11, 2020·Nature Communications·Marc D RyserDarryl Shibata
Jun 19, 2019·Nature Genetics·Zheng HuChristina Curtis
May 27, 2020·Nature Genetics·Johannes G ReiterKamila Naxerova
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Oct 18, 2020·Biomedicines·Ugo TestaElvira Pelosi
Apr 8, 2021·Nature Communications·Jeffrey WestAlexander R A Anderson

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