Minimal barriers to invasion during human colorectal tumor growth.

Nature Communications
Marc D RyserDarryl Shibata

Abstract

Intra-tumoral heterogeneity (ITH) could represent clonal evolution where subclones with greater fitness confer more malignant phenotypes and invasion constitutes an evolutionary bottleneck. Alternatively, ITH could represent branching evolution with invasion of multiple subclones. The two models respectively predict a hierarchy of subclones arranged by phenotype, or multiple subclones with shared phenotypes. We delineate these modes of invasion by merging ancestral, topographic, and phenotypic information from 12 human colorectal tumors (11 carcinomas, 1 adenoma) obtained through saturation microdissection of 325 small tumor regions. The majority of subclones (29/46, 60%) share superficial and invasive phenotypes. Of 11 carcinomas, 9 show evidence of multiclonal invasion, and invasive and metastatic subclones arise early along the ancestral trees. Early multiclonal invasion in the majority of these tumors indicates the expansion of co-evolving subclones with similar malignant potential in absence of late bottlenecks and suggests that barriers to invasion are minimal during colorectal cancer growth.

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Citations

Jul 8, 2020·Nature Genetics·Trevor A Graham, Darryl Shibata
Oct 18, 2020·Biomedicines·Ugo TestaElvira Pelosi
Nov 9, 2020·Human Pathology·Kyriakos ChatzopoulosGeorge Fountzilas
Feb 9, 2021·Cancer Metastasis Reviews·Michaël NoëRalph H Hruban
Apr 8, 2021·The Journal of Pathology·Norman SalomaoRobin Fahraeus
Jun 3, 2021·Genes & Development·Jiexi LiRonald A DePinho

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Methods Mentioned

BETA
saturation microdissection
exome sequencing
saturation microdissections
genotyping

Software Mentioned

Rtsne
SNE
phangorn
R
R Foundation for Statistical Computing

Related Concepts