Minimal barriers to invasion during human colorectal tumor growth

Marc D. Ryser (), Diego Mallo, Allison Hall, Timothy Hardman, Lorraine M. King, Sergei Tatishchev, Inmaculada C. Sorribes, Carlo C. Maley, Jeffrey R. Marks, E. Shelley Hwang and Darryl Shibata ()
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Marc D. Ryser: Duke University Medical Center
Diego Mallo: Arizona State University
Allison Hall: Duke University Medical Center
Timothy Hardman: Duke University Medical Center
Lorraine M. King: Duke University Medical Center
Sergei Tatishchev: University of Southern California Keck School of Medicine
Inmaculada C. Sorribes: Duke University
Carlo C. Maley: Arizona State University
Jeffrey R. Marks: Duke Cancer Institute
E. Shelley Hwang: Duke Cancer Institute
Darryl Shibata: University of Southern California Keck School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14908-7

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