Effects of tumor-originating niches on intra-tumor heterogeneity

Intra-tumor heterogeneity plays a crucial role during tumor initiation and progression. In practice, information about the genetic diversity in tumors is needed for developing individual therapies. However, there are still open questions in which manner intra-tumor heterogeneity evolves throughout tumor progression. In particular, it is unclear to which extent the architecture of the originally healthy tissue determines spatial patterns of intra-tumor heterogeneity. In this context, recent studies on the competition between tumor cells and wild-type cells lead to the concept of tumor-originating niches: Niches consist of a few cells whose competition during tumor initiation may predetermine the heterogeneity of the macroscopic, detectable tumor [1]. We study effects of tumor-originating niches on intra-tumor heterogeneity of the observed tumor and contrast them with the classical approach, where a tumor grows from a single cell. We examine in which manner mutations are spatially distributed throughout a tumor under presence and absence of tumor-originating niches. More precisely, we analyze the corresponding time scales of tumor initiation and identify spatial patterns of intra-tumor heterogeneity. To accomplish this, we use stochastic cellular automata and Markov theory for modeling, simulation and analysis. Understanding the spatial distribution of intra-tumor heterogeneity which originate from niches will contribute to more reliable prognoses in cancer therapy.