Saint-Antoine Hospital - Kourilsky Building – 3rd floor
34 rue Crozatier - 75571 paris cedex 12 - France
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. Consequences of the Hsp110DE9 mutation in tumorigenesis and the 5-fluorouracil-based chemotherapy response in Msh2-deficient mice. Noel K, Bokhari A, Bertrand R, Renaud F, Bourgoin P, Cohen R, Svrcek M, Joly AC, Duval A, Collura A. Cell Mol Life Sci. 2022 Jun 1;79(6):332. doi: 10.1007/s00018-022-04293-3.PMID: 35648235.
2. 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
3. [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
4. 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
5. 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
6. 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)
7. 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)
8. 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
9. 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, Qian K, Ho P, Malinowski S, Taquet L, Jones RE, Shetty A, Chow KH, Sharaf R, Pavlick D, Albacker LA, Younan N, Baldini C, Verreault M, Giry M, Guillerm E, Ammari S, Beuvon F, Mokhtari K, Alentorn A, Dehais C, Houillier C, Laigle-Donadey F, Psimaras D, Lee EQ, Nayak L, McFaline-Figueroa JR, Carpentier A, Cornu P, Capelle L, Mathon B, Barnholtz-Sloan JS, Chakravarti A, Bi WL, Chiocca EA, Fehnel KP, Alexandrescu S, Chi SN, Haas-Kogan D, Batchelor TT, Frampton GM, Alexander BM, Huang RY, Ligon AH, Coulet F, Delattre JY, Hoang-Xuan K, Meredith DM, Santagata S, Duval A, Sanson M, Cherniack AD, Wen PY, Reardon DA, Marabelle A, Park PJ, Idbaih A, Beroukhim R, Bandopadhayay P, Bielle F, Ligon KL. Nature. 2020 Apr;580(7804):517-523. doi: 10.1038/s41586-020-2209-9. PMID: 32322066
10. Identification of Positively and Negatively Selected Driver Gene Mutations Associated With Colorectal Cancer With Microsatellite Instability. Jonchere V, Marisa L, Greene M, Virouleau A, Buhard O, Bertrand R, Svrcek M, Cervera P, Goloudina A, Guillerm E, Coulet F, Landman S, Ratovomanana T, Job S, Ayadi M, Elarouci N, Armenoult L, Merabtene F, Dumont S, Parc Y, Lefèvre JH, André T, Fléjou JF, Guilloux A, Collura A, de Reyniès A, Duval A. Cell Mol Gastroenterol Hepatol. 2018 Jun 13;6(3):277-300. doi: 10.1016/j.jcmgh.2018.06.002. PMID: 30116770
11. Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas. Lupinacci RM, Goloudina A, Buhard O, Bachet JB, Maréchal R, Demetter P, Cros J, Bardier-Dupas A, Collura A, Cervera P, Scriva A, Dumont S, Hammel P, Sauvanet A, Louvet C, Delpéro JR, Paye F, Vaillant JC, André T, Closset J, Emile JF, Van Laethem JL, Jonchère V, Abd Alsamad I, Antoine M, Rodenas A, Fléjou JF, Dusetti N, Iovanna J, Duval A, Svrcek M. Gastroenterology. 2018 Mar;154(4):1061-1065. doi: 10.1053/j.gastro.2017.11.009. PMID: 29158190
12. The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors. Marisa L, Svrcek M, Collura A, Becht E, Cervera P, Wanherdrick K, Buhard O, Goloudina A, Jonchère V, Selves J, Milano G, Guenot D, Cohen R, Colas C, Laurent-Puig P, Olschwang S, Lefèvre JH, Parc Y, Boige V, Lepage C, André T, Fléjou JF, Dérangère V, Ghiringhelli F, de Reynies A, Duval A. J Natl Cancer Inst. 2018 Jan 1;110(1). doi: 10.1093/jnci/djx136. PMID: 28922790
13. HSP110 T17 simplifies and improves the microsatellite instability testing in patients with colorectal cancer. Buhard O, Lagrange A, Guilloux A, Colas C, Chouchène M, Wanherdrick K, Coulet F, Guillerm E, Dorard C, Marisa L, Bokhari A, Greene M, El-Murr N, Bodo S, Muleris M, Sourouille I, Svrcek M, Cervera P, Blanché H, Lefevre JH, Parc Y, Lepage C, Chapusot C, Bouvier AM, Gaub MP, Selves J, Garrett K, Iacopetta B, Soong R, Hamelin R, Garrido C, Lascols O, André T, Fléjou JF, Collura A, Duval A. J Med Genet. 2016 Jun;53(6):377-84. doi: 10.1136/jmedgenet-2015-103518. PMID: 26831756
14. Azathioprine May Not be Associated With Development of Colorectal Tumors With Microsatellite Instability in Patients With Inflammatory Bowel Disease.Svrcek M, Beaugerie L, Kirchgesner J, Dumont S, Muleris M, Bodo S, Dartigues P, Lascols O, Seksik P, Cosnes J, Fléjou JF, Duval A. Am J Gastroenterol. 2016 Jan;111(1):149-51. doi: 10.1038/ajg.2015.406. PMID: 26785668
15. Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents. Bodo S, Colas C, Buhard O, Collura A, Tinat J, Lavoine N, Guilloux A, Chalastanis A, Lafitte P, Coulet F, Buisine MP, Ilencikova D, Ruiz-Ponte C, Kinzel M, Grandjouan S, Brems H, Lejeune S, Blanché H, Wang Q, Caron O, Cabaret O, Svrcek M, Vidaud D, Parfait B, Verloes A, Knappe UJ, Soubrier F, Mortemousque I, Leis A, Auclair-Perrossier J, Frébourg T, Fléjou JF, Entz-Werle N, Leclerc J, Malka D, Cohen-Haguenauer O, Goldberg Y, Gerdes AM, Fedhila F, Mathieu-Dramard M, Hamelin R, Wafaa B, Gauthier-Villars M, Bourdeaut F, Sheridan E, Vasen H, Brugières L, Wimmer K, Muleris M, Duval A; European Consortium “Care for CMMRD”. Gastroenterology. 2015 Oct;149(4):1017-29.e3. doi: 10.1053/j.gastro.2015.06.013. PMID: 26116798
16. Patients with colorectal tumors with microsatellite instability and large deletions in HSP110 T17 have improved response to 5-fluorouracil–based chemotherapy. Collura A, Lagrange A, Svrcek M, Marisa L, Buhard O, Guilloux A, Wanherdrick K, Dorard C, Taieb A, Saget A, Loh M, Soong R, Zeps N, Platell C, Mews A, Iacopetta B, De Thonel A, Seigneuric R, Marcion G, Chapusot C, Lepage C, Bouvier AM, Gaub MP, Milano G, Selves J, Senet P, Delarue P, Arzouk H, Lacoste C, Coquelle A, Bengrine-Lefèvre L, Tournigand C, Lefèvre JH, Parc Y, Biard DS, Fléjou JF, Garrido C, Duval A. Gastroenterology. 2014 Feb;146(2):401-11.e1. doi: 10.1053/j.gastro.2013.10.054. PMID: 24512910
17. Extensive characterization of sphere models established from colorectal cancer cell lines. Collura A, Marisa L, Trojan D, Buhard O, Lagrange A, Saget A, Bombled M, Méchighel P, Ayadi M, Muleris M, de Reynies A, Svrcek M, Fléjou JF, Florent JC, Mahuteau-Betzer F, Faussat AM, Duval A. Cell Mol Life Sci. 2013 Feb;70(4):729-42. doi: 10.1007/s00018-012-1160-9. PMID: 23007843
18. Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis. Dorard C, de Thonel A, Collura A, Marisa L, Svrcek M, Lagrange A, Jego G, Wanherdrick K, Joly AL, Buhard O, Gobbo J, Penard-Lacronique V, Zouali H, Tubacher E, Kirzin S, Selves J, Milano G, Etienne-Grimaldi MC, Bengrine-Lefèvre L, Louvet C, Tournigand C, Lefèvre JH, Parc Y, Tiret E, Fléjou JF, Gaub MP, Garrido C, Duval A. Nat Med. 2011 Sep 25;17(10):1283-9. doi: 10.1038/nm.2457. PMID: 21946539. doi: 10.1038/nm.2457. PMID: 21946539
MSI tumors (for MicroSatellite Instability) are a type of tumors with genomic alterations due to a defect in the DNA repair system. To better understand the origin of these cancers and the consequences of their genomic characteristics, notably the anti-tumor treatment responces, the SiRIC Curamus, the MSI and Cancer research team of the Saint-Antoine Research Center present you this MSI team research vulgarisation video.
(click on the image to see the video)
INSERM
Kourilsky Building
34 rue Crozatier - 75012 Paris
France
Sorbonne Université Medicine
Saint-Antoine Site
27 rue Chaligny - 75012 Paris
France
