«Pendant des siècles, la Médecine s’est préoccupée de soigner. Aujourd’hui elle s'est donnée comme but de prévenir plutôt que de guérir.»
Pr Jean Dausset, Prix Nobel de Médecine, 1980
La Fondation Jean Dausset - Centre d’Etude du Polymorphisme Humain participe aux efforts nationaux et internationaux de recherche pour mieux déterminer le rôle du polymorphisme génétique chez l’Homme, tout particulièrement dans les maladies complexes, pour mieux les comprendre, les diagnostiquer et participer au développement d’une médecine personnalisée.

Foundation ARC 2019 Project: Development of new molecular approaches

for the detection of microsatellite instability in cancer

    Principal Investigator: Alexandre How Kit, Fondation Jean Dausset - CEPH

Microsatellite instability (MSI) is a genetic alteration caused by the loss of function of the DNA repair system (MMR), which is characterized by the accumulation of mutations in microsatellites. MSI was originally described in colorectal cancer (CRC) in which 15% of tumors exhibit this alteration, which correlates with better patient survival. In addition, 3-5% of CRCs occur in the context of hereditary Lynch syndrome and are of MSI type. Detection of MSI is therefore recommended for all patients with CRCs as a first screening for Lynch syndrome. More recently, the presence of MSI has been demonstrated in many different types of cancer by pan-genomic analyses, where the MSI phenotype is associated with better patient survival. MSI has also been shown to predict the efficacy of immune checkpoint inhibitor (ICI) therapy in solid tumors. Thus, the U.S. F.D.A. authorized the use of this genetic alteration as a universal biomarker for the administration of ICI immunotherapies to patients with all types of solid cancers.

However, the current gold standard approach for MSI testing in CRC presents poor performances for the detection of MSI in other types of cancers and also lacks analytical sensitivity, failing to detect MSI in some samples. Unlike other types of genetic alterations found in cancer, only a small number of molecular approaches have been so far developed to improve MSI detection in cancer. The Foundation ARC project of the Foundation Jean Dausset - CEPH aims (i) to develop new ultra-sensitive molecular approaches for the diagnosis of MSI in samples with low tumor DNA content, (ii) to evaluate and compare these approaches with the reference method and (iii) allow the detection of MSI in new clinical applications of major interest.

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