Modelling the Effects of Genetic Changes in Tumour Progression

摘要

Tumours can be considered a set of cells that accumulate genetic and epigenetic alterations. According to the Multi-stage Hit theory, the transformation of a normal into a tumour cell involves a number of limiting events that occur in a number of discrete stages (driver mutations). However, not all mutations that occur in the cell are directly involved in the development of cancer and some probably do not contribute in any way (passenger mutations). Moreover, the process of tumour evolution is punctuated by selection of advantageous mutations and clonal expansions. Actually, it is not known how many limiting-events, i.e., how many driver mutations are necessary or sufficient to promote a carcinogenic process. This conjecture should be explored and tested - mathematically and statistically, with the availability of genomic data on databanks. In this work, we explore the model proposed by Bozic and collaborators (2010) that describes the evolution of the tumour according to a Galton-Watson process. Besides, the model gives the relation between the numbers of passenger mutations giving a specific number of driver mutations. We intend to explore some of the model parameters and test some premises about the number of drive mutations and selective advantage, comparing the simulation results with genomic data from colorectal cancer patients. The genomic data was obtained from the DBMutation (http://www.bioinformatics-brazil.org/dbmutation/), a comprehensive database for genomic mutations in cancer. We expect that correlations between driver mutations and the time evolution of tumour process will facilitate the interpretation of genomic information, to make them useful and applicable to clinical oncology.