Minimal barriers to invasion during human colorectal tumor growth.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ryser, MD; Mallo, D; Hall, A; Hardman, T; King, LM; Tatishchev, S; Sorribes, IC; Maley, CC; Marks, JR; Hwang, ES; Shibata, D

Published Date

  • March 9, 2020

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 1280 -

PubMed ID

  • 32152322

Pubmed Central ID

  • PMC7062901

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-14908-7

Language

  • eng

Conference Location

  • England