The research group of Professor Isao Mimori of Kyushu University, together with the University of Tokyo and Oita University, has constructed a new evolutionary model that explains the acquisition principle of intratumoral diversity of colorectal cancer.The development of next-generation cancer therapies that overcome intractable cancers with intratumoral diversity is expected.
In this study, in addition to the advanced colorectal cancer data obtained in the previous study (2016), comprehensive gene mutation data from multiple sites of each tumor obtained from 10 patients with early-stage colorectal cancer using the next-generation sequencer. Was obtained, and both data were combined and mathematical statistical analysis was performed using a supercomputer.
Gene mutations that play a directly important role in the development and progression of cancer are called "driver mutations."As a result of this analysis, in early stage cancer, multiple driver mutations that favor the growth and survival of cancer cells are scattered in one tumor, resulting in "Darwinian evolution" that undergoes natural selection.
On the other hand, mutations that occur naturally regardless of positive or negative natural selection are called "neutral mutations", but in advanced cancer, innumerable neutral mutations that do not affect the growth and survival of cancer cells accumulate. "Neutral evolution" has created intratumoral diversity, revealing that evolutionary patterns are changing.It was also clarified that there are significantly more abnormal chromosome copy numbers in advanced cancer than in early stage cancer, and it was found that the abnormal chromosome copy number may be the trigger for this "evolutionary shift".
The results of this research are expected to be the basis for the development of next-generation cancer therapies that overcome intractable cancers with intratumoral diversity.
Paper information:[Nature Communications] A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer