New genes implicated in liver cancer identified: another step towards personalised medicine

INSERM: Hepato Cellular Carcinoma is the second most common cause of death from cancer in the world and is linked to various pre-existing problems such as hepatitis B and C infections, excessive alcohol consumption, high iron levels and obesity-related chronic hepatitis. French researchers have used high-throughput sequencing techniques to study cancer linked to excessive alcohol consumption and obesity in particular, seeking to identify the mutations and rearrangements implicated in tumour genesis and the progression and resistance of the disease. The team’s research, published in the journal Nature Genetics on 30 March 2015, demonstrates:
- that there is a link between individuals’ exposure to risk factors during their lives (alcohol, tobacco, food toxins) and the DNA mutations found in their tumours;

- that each tumour is the product of a unique combination of genetic changes, involving around 40 genes on average. The complexity of this genetic diversity explains in large part the problem of resistance to current treatments. However, using this new gene catalogue, for almost 1 in 3 cases a genetic change can be identified that could be targeted by an anticancer drug. The efficacy of drugs prescribed in this way on the basis of genome alterations will need to be demonstrated in next generation ‘genome-based clinical trials’, which will form the basis for the forthcoming ICGC2 project;
- lastly, these studies have identified the initial mutations behind the malignant changes in liver cells . This finding should help to improve early diagnosis and to detect which patients are most at risk of developing liver cancer.

The research was coordinated and funded by the National Cancer Institute (INCa) and was carried out in close collaboration with Inserm. It also benefited from:
- scientific collaboration with Prof. Josep Llovet’s team in Barcelona and Prof. Mike Stratton’s team in Cambridge;
- support from Paris Descartes, Paris Diderot and Paris 13 Universities and Paris Saint-Louis Haematology Institute;
- support from the French Cancer Research Association (ARC), through the PAIR CHC project, funded jointly with INCa, and support from the EU HEPTROMIC project (FP7);
- collaboration with the National Liver Tumour Biobank (CRB), coordinated by Bruno Clément with clinicians and histopathologists from Bordeaux University Hospital (Paulette Bioulac-Sage, Jean-Frédéric Blanc, Charles Balabaud) and Créteil University Hospital (Julien Calderaro, Alexis Laurent);
- all the high throughput sequencing was carried out by IntegraGen (Evry, France);
- the support of the National Cancer League (Ligue contre le Cancer-labelled team).