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Normal tissue architecture determines the evolutionary course of cancer.

ABSTRACT: Cancer growth can be described as a caricature of the renewal process of the tissue of origin, where the tissue architecture has a strong influence on the evolutionary dynamics within the tumor. Using a classic, well-studied model of tumor evolution (a passenger-driver mutation model) we systematically alter spatial constraints and cell mixing rates to show how tissue structure influences functional (driver) mutations and genetic heterogeneity over time. This approach explores a key mechanism behind both inter-patient and intratumoral tumor heterogeneity: competition for space. Time-varying competition leads to an emergent transition from Darwinian premalignant growth to subsequent invasive neutral tumor growth. Initial spatial constraints determine the emergent mode of evolution (Darwinian to neutral) without a change in cell-specific mutation rate or fitness effects. Driver acquisition during the Darwinian precancerous stage may be modulated en route to neutral evolution by the combination of two factors: spatial constraints and limited cellular mixing. These two factors occur naturally in ductal carcinomas, where the branching topology of the ductal network dictates spatial constraints and mixing rates.

SUBMITTER: West J

PROVIDER: S-EPMC8024392 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Normal tissue architecture determines the evolutionary course of cancer.

West Jeffrey J Schenck Ryan O RO Gatenbee Chandler C Robertson-Tessi Mark M Anderson Alexander R A ARA

Nature communications 20210406 1

Cancer growth can be described as a caricature of the renewal process of the tissue of origin, where the tissue architecture has a strong influence on the evolutionary dynamics within the tumor. Using a classic, well-studied model of tumor evolution (a passenger-driver mutation model) we systematically alter spatial constraints and cell mixing rates to show how tissue structure influences functional (driver) mutations and genetic heterogeneity over time. This approach explores a key mechanism be ...[more]

PMID: 33824323

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Normal tissue architecture determines the evolutionary course of cancer.

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Normal tissue architecture determines the evolutionary course of cancer.

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