Population dynamics is a cancer driver

Author:

dos Santos Oliveira Mariana12,de C Griebeler Marcelo3,Henz Bernardo45,dos Santos Filipe Ferreira67,Guardia Gabriela D A6,Conceição Helena B68,Galante Pedro A F67ORCID,Minussi Darlan C12,Oliveira Manuel M4,Lenz Guido12ORCID

Affiliation:

1. Departamento de Biofísica, Universidade Federal do Rio Grande do Sul (UFRGS) , Av. Bento Gonçalves, 9500, 91501-970, Porto Alegre, RS , Brazil

2. Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS) , Av. Bento Gonçalves, 9500, 91501-970, Porto Alegre, RS , Brazil

3. Departamento de Economia e Relações Internacionais, Universidade Federal do Rio Grande do Sul (UFRGS) , Av. João Pessoa, 52, 90040-000, Porto Alegre, RS , Brazil

4. Instituto de Informática, Universidade Federal do Rio Grande do Sul (UFRGS) , Av. Bento Gonçalves, 9500, 91501-970, Porto Alegre, RS , Brazil

5. Instituto Federal Farroupilha, Campus Alegrete , Rodovia RS-377, s/n, 97555-000 Alegrete, RS , Brazil

6. Centro de Oncologia Molecular, Hospital Sirio-Libanes , Prof Daher Cutait, 69, 013080-60, São Paulo, SP , Brazil

7. Departamento de Bioquimica, Instituto de Quimica, Universidade de São Paulo , Av. Prof. Lineu Prestes, 748, 05508-090, São Paulo, SP , Brazil

8. Interunidades em Bioinformática, Universidade de São Paulo , R. do Matão, 1010, 05508-090, São Paulo, SP , Brazil

Abstract

Abstract Most tissues are continuously renovated through the division of stem cells and the death of old or damaged cells, which is known as the cell turnover rate (CTOR). Despite being in a steady state, tissues have different population dynamics thus producing diverse clonality levels. Here, we propose and test that cell population dynamics can be a cancer driver. We employed the evolutionary software esiCancer to show that CTOR, within a range comparable to what is observed in human tissues, can amplify the risk of a mutation due to ancestral selection (ANSEL). In a high CTOR tissue, a mutated ancestral cell is likely to be selected and persist over generations, which leads to a scenario of elevated ANSEL profile, characterized by few niches of large clones, which does not occur in low CTOR. We found that CTOR is significantly associated with the risk of developing cancer, even when correcting for mutation load, indicating that population dynamics per se is a cancer driver. This concept is central to understanding cancer risk and for the design of new therapeutic interventions that minimizes the contribution of ANSEL in cancer growth.

Funder

FAPERGS

Publisher

Oxford University Press (OUP)

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