restrictive and permissive effects of the genome architecture on lineage
selection during somatic cancer evolution
Most clinically distinguishable malignant
tumors are characterized by specific mutations, specific patterns of
chromosomal rearrangements and a predominant mechanism of genetic
but it remains unsolved whether modifications of cancer genomes can be
explained solely by mutations and positive or negative selection through
It has been suggested that internal dynamics of
genomic modifications as opposed to the external evolutionary forces
significant and complex impact on Darwinian species evolution.
situation can be expected for somatic cancer evolution as molecular key
mechanisms encountered in species evolution also constitute prevalent
mechanisms in human cancers.
The principal hypothesis is that permissive or
restrictive effects of the genome architecture on lineage selection
somatic cancer evolution exist and have an impact which is comparable in
magnitude to the effects of selection by the tumor microenvironment.
The goal of the project is to develop this approach from a systems
concept to applicable bioinformatic tools for designing new anti-cancer
The starting point is a simulation of somatic cancer evolution with
unequal sister chromatid exchange as only mutation mechanism (CSim-2000 6.14).
The program package can be downloaded under the GNU Free Documentation License: