A systems approach defining constraints of the genome architecture on lineage selection and evolvability during somatic cancer evolution

摘要: Summary Most clinically distinguishable malignant tumors are characterized by specific mutations, patterns of chromosomal rearrangements and a predominant mechanism genetic instability but it remains unsolved whether modifications cancer genomes can be explained solely mutations selection through the microenvironment. It has been suggested that internal dynamics genomic as opposed to external evolutionary forces have significant complex impact on Darwinian species evolution. A similar situation expected for somatic evolution molecular key mechanisms encountered in also constitute prevalent mutation human cancers. This assumption is developed into systems approach carcinogenesis which focuses possible inner constraints genome architecture lineage during The proposed considered an analogy concept evolvability principal hypothesis permissive or restrictive effects exist measurable impact. postulates three classes evolution: i) mediated changes fitness cells lineage, ii) probabilities iii) gene designation physical functional redundancy. Physical redundancy copy number identical sequences. Functional regulatory element defined different elements, regardless number, coding same biological function within cell. Complex interactions may when multiple possibly manifest themselves at disparate times progression stages. Dissection putative mediating exerted provide algorithm understanding predicting well modifying individual patients.