Stem cell proliferation: towards a better understanding of cell processes linked to cancer?

November 26 2008

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Stem cell proliferation: towards a better understanding of cell processes linked to cancer?In a study published on 24 November in the review Nature Biotechnology, Anselme Perrier and his team at Istem identified a recurring abnormality in the genome of human embryonic stem cells left for too long in culture. Whether by chance or not, this same abnormality is found in a certain number of cancers. This discovery suggests that the same process may cause the proliferation of both stem cells and cancer cells.These studies were supported in particular by the AFM (FrenchMuscular Dystrophy Association) thanks to Téléthon donations.

The development of cancer is a "multi-stage" process following the accumulation of mutations in the genes involved in controlling cell proliferation. These genetic changes lead to the progressive transformation of a normal cell into a derivative malignant cell. Abnormalities in the number and structure of chromosomes (karyotypic abnormalities) are frequently observed in cancers.

Embryonic stem cells are able to multiply more or less limitlessly and to differentiate into all the cell types of the human body (pluripotent cells). In vitro, it is possible to maintain them in an undifferentiated state. Under precise culture conditions it is possible to induce differentiation into a given cell type (neurons, blood cells, heart cells etc).

ES (embryo stem) cells on feeders and cells ready to be differentiated. These pluripotent stem cells can form all the tissues in the living organism (over 200 types of cell tissue).

ES (embryo stem) cells on feeders and cells ready to be differentiated. These pluripotent stem cells can form all the tissues in the living organism (over 200 types of cell tissue).

In this study coordinated by the Inserm scientist Anselme Perrier, regular control of the integrity of the human embryonic stem cell genome made it possible to identify a highly unstable region of the human genome, located on chromosome 20.

A supernumerary copy of a fragment of chromosome 20 repeatedly occurs in human embryonic stem cells maintained for a long period in vitro in an undifferentiated state. This region has already been found to be amplified in many cancers, in particular in breast, bladder, lung, and liver cancers, melanoma and cervical cancer. Studies have shown that the genetic instability of this amplified region was an important event in tumour progression.

Human embryonic stem cells may therefore improve our understanding of the early events involved in tumour progression. They also have the advantage that it is possible to study the role of the region identified by Inserm researchers in a background where there are no other genetic abnormalities.

Human embryonic stem cells
In France, most teams authorised by the Biomedecine Agency to work on hES cells belong to academic research, and mainly to Inserm (22 projects out of 35, and 15 of the 26 authorised teams). I-Stem, set up on 1 January, 2005, is a research and development centre dedicated to the study of the therapeutic potential of these cells and their application to rare genetic diseases. AFM, Inserm and Evry-Val-d'Essonne University are the founder members.
Embryonic stem cells are obtained from the human embryo at the very first stages of its development, only a few days after fertilisation. These cells are "pluripotent" : they may reproduce indefinitely (self-renewal), proliferate in culture and differentiate into more than 200 tissue types. During development, they may give rise to all the tissues of the body. Their potential biological and medical applications are currently thought to depend on this capacity.


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Source
"Human embryonic stem cells reveal recurrent genomic instability at 20q11.21"
Nature Biotechnology

Researcher's contact
Anselme Perrier
Neurodegenerative Diseases Team
Inserm /UEVE UMR 861, I-STEM, AFM
Tel: +33 1 69 90 85 23

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