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Focus on : Intra-tumour diversification in colorectal cancer at the single-cell level - Published on 19 04 2018

A few days ago, an interesting study focusing on bowel cancer heterogeneity was published in Nature. This work is a collaboration of from Hans Clever & Michael R Straton labs. This very innovative work consist in a characterization of organoids derived from multiple single cells from three colorectal cancers compared to  the adjacent normal intestinal crypts. The scientists used the latest single cell and organoid technologies to understand the mutational processes involved in this tumors. The results indicates that colorectal cancer cells experience substantial increases in somatic mutation rate compared to normal colorectal cells, and that genetic diversification of each cancer is accompanied by pervasive, stable and inherited differences in the biological states of individual cancer cells.


Abstract

Every cancer originates from a single cell. During expansion of the neoplastic cell population, individual cells acquire genetic and phenotypic differences from each other. Here, to investigate the nature and extent of intra-tumour diversification, we characterized organoids derived from multiple single cells from three colorectal cancers as well as from adjacent normal intestinal crypts. Colorectal cancer cells showed extensive mutational diversification and carried several times more somatic mutations than normal colorectal cells. Most mutations were acquired during the final dominant clonal expansion of the cancer and resulted from mutational processes that are absent from normal colorectal cells. Intra-tumour diversification of DNA methylation and transcriptome states also occurred; these alterations were cell-autonomous, stable, and followed the phylogenetic tree of each cancer. There were marked differences in responses to anticancer drugs between even closely related cells of the same tumour. The results indicate that colorectal cancer cells experience substantial increases in somatic mutation rate compared to normal colorectal cells, and that genetic diversification of each cancer is accompanied by pervasive, stable and inherited differences in the biological states of individual cancer cells.


Read the full paper : http://www.nature.com.gate2.inist.fr/articles/s41586-018-0024-3

Remember that we organize a workshop on organoïds for the study of heterogeneity in tumors the next 16th May in Paris.

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This French program is organized by ITMO Cancer, in collaboration with ITMO BCDE (Cell Biology, Development and Evolution) and ITMO Technologies for Health of the National Alliance for Life Sciences and Health (AVIESAN) with the National Cancer Institute (INCA) and Inserm within the framework of the Cancer Plan. Operational management is entrusted to Inserm.
It was launch in order to develop a critical mass of resources and skills in order to conduct interdisciplinary research projects in the field of functional heterogeneity of cellular tumor relations in their ecosystem: the "HTE Program".

Initiation of HTE Program