Instabilité des microsatellites et cancers

Alex Duval
Chef(s) d'équipe(s) : Alex Duval
Contact administratif : Alhamid Saïdi

Hôpital Saint-Antoine – Bâtiment Kourilsky – 3ème étage
34 rue Crozatier – 75571 PARIS cedex 12

Professeurs, Maîtres de conférence, Chercheurs, Cliniciens
Post-doctorants, Chercheurs contractuels, Éméritat, Bénévolat
DORARD Coralie
Ingénieurs, Techniciens
Doctorants, Master

Our team has been created on January 1st, 2006, initially as a monothematic research unit (UMRS 762). In 2009, it has joined the Saint-Antoine Research Centre located in this Hospital that was recently created by the INSERM and the University Pierre and Marie Curie. The topics for our research group are focused on the study of mismatch repair (MMR)-deficient human tumors that develop through a particular molecular pathway characterized by the genetic instability of numerous microsatellite repeat sequences throughout the genome (MSI tumors). Since founded, the research interest of our lab is the analysis of the genetics of MSI tumors whatever their localization. The overall aim of our activity is to investigate important pathophysiological aspects of MSI carcinogenesis. Questions and hypothesis, on the fundamental and clinical sides, related to this particular tumor type are deduced from the analysis of causes and functional consequences of the microsatellite instability process characteristics of these tumors. These last ten years, we have built and exploited a unique collection of biological tools, mouse models, sample collections, clinical databases and techniques that have been designed or adapted by ourselves and collaborators for the study of MSI cancers. Translational research topics have been developed in order to gain maximum benefit from our findings. This allowed the discovery of new risk factors, biomarkers, and diagnostic tools of clinical interest for patients suffering from MSI cancers.

1. Performance of Next-Generation Sequencing for the Detection of Microsatellite Instability in Colorectal Cancer With Deficient DNA Mismatch Repair. Ratovomanana T, Cohen R, Svrcek M, Renaud F, Cervera P, Siret A, Letourneur Q, Buhard O, Bourgoin P, Guillerm E, Dorard C, Nicolle R, Ayadi M, Touat M, Bielle F, Sanson M, Le Rouzic P, Buisine MP, Piessen G, Collura A, Fléjou JF, de Reyniès A, Coulet F, Ghiringhelli F, André T, Jonchère V, Duval A. Gastroenterology. 2021 Sep;161(3):814-826.e7. doi: 10.1053/j.gastro.2021.05.007. PMID: 33992635

2. [Microsatellite instability and cancer: from genomic instability to personalized medicine]. Collura A, Lefevre JH, Svrcek M, Tougeron D, Zaanan A, Duval A. Med Sci (Paris). 2019 Jun-Jul;35(6-7):535-543. doi: 10.1051/medsci/2019093. PMID: 31274083

3. Association of Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer With Misdiagnosis of Microsatellite Instability or Mismatch Repair Deficiency Status. Cohen R, Hain E, Buhard O, Guilloux A, Bardier A, Kaci R, Bertheau P, Renaud F, Bibeau F, Fléjou JF, André T, Svrcek M, Duval A. JAMA Oncol. 2019 Apr 1;5(4):551-555. doi: 10.1001/jamaoncol.2018.4942. PMID: 30452494

4. Targeting nonsense-mediated mRNA decay in colorectal cancers with microsatellite instability. Bokhari A, Jonchere V, Lagrange A, Bertrand R, Svrcek M, Marisa L, Buhard O, Greene M, Demidova A, Jia J, Adriaenssens E, Chassat T, Biard DS, Flejou JF, Lejeune F, Duval A, Collura A. Oncogenesis. 2018 Sep 19;7(9):70. doi: 10.1038/s41389-018-0079-x. PMID: 30228267

5. MSI/MMR-deficient tumor diagnosis: Which standard for screening and for diagnosis? Diagnostic modalities for the colon and other sites: Differences between tumors. Svrcek M, Lascols O, Cohen R, Collura A, Jonchère V, Fléjou JF, Buhard O, Duval A. Bull Cancer. 2019 Feb;106(2):119-128. doi: 10.1016/j.bulcan.2018.12.008. PMID: 30713006 (Review)

6. Pancreatic ductal adenocarcinoma harboring microsatellite instability / DNA mismatch repair deficiency. Towards personalized medicine. Lupinacci RM, Bachet JB, André T, Duval A, Svrcek M. Surg Oncol. 2019 Mar;28:121-127. doi: 10.1016/j.suronc.2018.11.019. PMID: 30851885 (Review)

7. Primary Resistance to Immune Checkpoint Inhibitors in Metastatic Colorectal Cancer-Beyond the Misdiagnosis-In Reply. Cohen R, Duval A, Svrcek M. JAMA Oncol. 2019 May 1;5(5):741. doi: 10.1001/jamaoncol.2019.0536. PMID: 30973609

8. Mechanisms and therapeutic implications of hypermutation in gliomas. Touat M, Li YY, Boynton AN, Spurr LF, Iorgulescu JB, Bohrson CL, Cortes-Ciriano I, Birzu C, Geduldig JE, Pelton K, Lim-Fat MJ, Pal S, Ferrer-Luna R, Ramkissoon SH, Dubois F, Bellamy C, Currimjee N, Bonardi J