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Analysis of 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 instability but it remains unsolved whether modifications of cancer genomes can be explained solely by mutations and positive or negative selection through the cancer microenvironment.

It has been suggested that internal dynamics of genomic modifications as opposed to the external evolutionary forces have a significant and complex impact on Darwinian species evolution.

A similar situation can be expected for somatic cancer evolution as molecular key mechanisms encountered in species evolution also constitute prevalent mutation mechanisms in human cancers.

The principal hypothesis is that permissive or restrictive effects of the genome architecture on lineage selection during 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 therapies.

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:

 

CSim-2000-6-14.zip


Improvements of this program or additional approaches for data mining of cancer genomes and cancer protein function networks are appreciated.