Repair-Dependent Competition Between Direct Driver Founding and Stochastic Tunneling Before Clonal Establishment
Year: 2026
Type: preprint
Abstract: DNA repair may change not only whether damaged cells survive but also which mutational route produces successful progression. We compare direct two-driver founding in a single division with sequential stochastic tunneling through a transient one-driver lineage. Founders arise from an endogenous homeostatic mutation–repair equilibrium and initiate branching processes stopped by extinction, an irreversible commitment event, or a finite clone-size bound- ary; only commitment before the other outcomes counts as success. At each fixed size boundary, both routes contribute at order V^2 in a rare independent- driver mutation expansion, with V held unchanged across repair comparisons. Exact finite-state coefficients establish a repair-induced reversal of the dominant route after averaging over the homeostatic founder mixture. An opportunity–turnover–establishment identity shows why improved cellular demography need not increase divisions eligible for a second hit. With lesion-dependent post-hit outcomes, a sharp criterion describes overshoot in the unbounded subcritical model, while certified finite-clone examples demonstrate re-entrant dominance. The resulting biological observable is a repair-dependent mixture of successful routes, distinct from clinical cancer incidence. MSC Classification: 92D15 , 60J80 , 60J35
Source: Research Square
Author: Benjamin Hardisty
Institution: VA Office of Research and Development
Language: English
Subfield: Mathematical Physics
Field: Mathematics
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7225628144