The Paris Cancer Institute CARPEM have strong dual routine and research activities in the genomics of solid tumors (mainly endocrine, gastro-intestinal, hepatic, thoracic, gynecological dermatological, urological tumors and sarcomas), and hematological malignancies. Altogether, biologist and pathologist analyzed samples of more than 3000 patients with cancer each years for the main genomic alterations and contributed therefore to a precision care of the patients. They have a strong activity in translational research, and they facilitated the rapid adoption of new tests in daily clinical practices
All these activities are structured around cancer multidisciplinary team meetings both for solid tumors (one in Cochin – Pr. E. Pasmant and one in HEGP – Pr H. Blons) and for hematological malignancies one on lymphoid diseases (Necker – Pr V.Asnafi), one on myeloid malignancies (Cochin – Pr. M. Fontenay) including members of the genomics of tumors program per organ as well as pathologist radiologist. These meetings follow the INCA national guidelines, and ESMO guidelines. These platforms are INCa-labelled since 2008 and somatic testing has been COFRAC-labelled for the subset of tests used in clinical settings.
Bioinformatics is organized around senior researchers (G. Assié, H. Blons, O. Kosmider, P. Laurent-Puig, E. Letouzé) with help of MOABI department in the SeQoia Platform led by Pr. M. Vidaud for whole genome and whole exome sequencing. The SIRIC CARPEM currently support two bioinformaticians to develop new pipelines.
Furthermore, since end of 2014 for solid tumors APHP tumor board was led by P. Laurent-Puig who set-up a program of exome and RNA sequencing for selected patients with colon, lung or rare cancers. This program is the forerunner of the “Tumor Board” France Genomic Medicine 2025 Plan, which set out the indications of whole genome sequencing, whole exome sequencing and RNA-sequencing for patients in therapeutic failure and rare cancers. These National programs are led by P. Laurent-Puig and Anne-Paule Gimenez-Roqueplo respectively. In Onco-hematology, the indications validated by the France genomic Medicine 2025 plan involving patients with acute leukemia in relapse and aggressive lymphomas
Remarkable features of this program:
The teams largely contribute to the molecular classification of their tumor of interest and discovered biomarkers or composite biomarkers for diagnosis and prognosis (Molecular classification of colon, renal, mesothelioma, hepatocellular carcinoma, T-acute lymphoblastic leukemia and myelodysplastic syndromes). They have made major contributions in the genomic field of solid and hematological cancers. They have strong activities in the translational research and the CARPEM research program facilitated the transfer into daily practice. They developed specific methods for detecting circulating tumor DNA in solid tumors by sequencing and implemented this in routine tests for lung and colon cancer.
Physicians, biologists and scientists involved in this program interacted strongly with in-site physicians highly renowned in the diagnosis of solid and hematological. They are involved in numerous national and international programs in their fields of expertise. They are also strongly involved in clinical and translational research of different programs of the SIRIC Carpem. Their activities encompass a wide variety of tumor types which included frequent and rare tumors. This research activity is either part of ancillary research within the framework of therapeutic trials, or of research further upstream, enabling the identification of new biomarkers.It benefits from national and European academic (Europe program H2020, INCA, PHRC, ANR), non-academic charities (ARC, Ligue) and industry funding. In particular, several teams coordinate or participate in major networks of research in France (Plan-cancer, 4 PRT-K programs, …) and in Europe (COMETE, FP7 TRIAGE, MDS-RIGHT, ICGC FR-Liver, Mantle Lymphoma Network).
Translational research involves 10 teams, 5 of wich are Inserm research teams, located to the PARCC, INEM, Imagine, Institut Cochin and the Cordeliers research centers.
The research teams led by Jérôme Bertherat (IC), Isabelle Cremer (CRC), Anne-Paule Gimenez-Roqueplo (PARCC), Pierre Laurent-Puig (CRC), Eric Pasmant (IC) and J. Zucman-Rossi (CRC) have main translational research fields about the genomics of solid tumors including rare endocrine tumors, lung cancer, sarcoma, paraganglioma, colon cancer, neurofibromatosis, mesothelioma, hepatocarcinoma and renal cancer in order to find prognostic and predictive markers of therapeutic responses.
J. Zucman-Rossi team by developing whole genome and exome sequencing together with RNAseq, identified several new oncogenes and tumor suppressors genes in human hepatocellular carcinoma (HCC). Translation to diagnostic, prognostic and identification of therapeutic targets is progressively performed for HCC and adenoma (Nault et al, 2017, Rebouissou et al, 2016). This team also contributes to decipher the molecular classification of clear-cell renal cell carcinomas (Verbiest et al, 2019). Furthermore Didier Jean in J Zucman-Rossi’s team has developed a molecular classification of mesothelioma and by using a deconvolution approach, refine the classification by considering the epithelioid-like and sarcomatoid-like components of the tumor (Tranchant et al, 2017; Blum et al, 2019).
AP Gimenez-Roqueplo and J Favier team performed an extensive genetic and genomic characterization of the largest international cohort of Pheochromocytomas and Paragangliomas (PPGL) patients and identified molecular signatures and oncogenic pathways associated with driver mutations (Fishbein et al, 2017 ; Ben Aim et al, 2019). Focusing on succinate dehydrogenase genes (SDH)-mutated tumors has revealed mechanisms explaining the metastatic phenotype. The development of a magnetic resonance spectroscopy imaging method for succinate detection allows exploring tumor masses before surgery (Lussey-Lepoutre et al, 2016).
J Bertherat and G Assié team performed the first integrated genomics study of Adrenocortical tumors (Zheng et al, 2016). Molecular classification revealed 2 major groups of cancers with specific gene expression profiles: one C1B group with good outcome and one C1A group with poor outcome. The C1B group can further be divided into 3 subgroups according to methylation and driver gene status (Jouinot et al, 2017). These results have allowed to develop molecular markers based on targeted methylation assay for ACC prognostication (Assié et al, 2019).
Laurent-Puig and V. Taly team has developed new technologies to characterize circulating tumor DNA (ctDNA), that can change clinical practices: (1) NGS routine test enables to detect alterations as low as 0.1% in plasma (Pécuchet et al, 2016a) (2) Detection of hypermethylation of WIF1 and NPY genes by ddPCR was developed as a universal ctDNA marker in colon cancer (Garrigou et al, 2016). These methods were validated in 3 prospective studies showing that the initial ctDNA concentration and its decrease during treatment is a prognostic marker in pancreatic (Pietrasz et al, 2017), lung (Pécuchet et al, 2016b) and colon cancer (Garlan et al, 2017,).
Finally, at the instigation of SIRIC CARPEM, several collaborative projects between the teams have been set up P Laurent-Puig H. Blons, K. Leroy and E. Pasmant have developed novel panel of genes for diagnosis in clinical setting of non-small cell lung cancer, colon cancer, and sarcoma (Legras et al, 2018; Tlemsani et al, 2018; 2019). In collaboration with I Cremer’s team, H Blons and D. Damotte developed a combined histomolecular algorithm to distinguish multiple primary tumors from metastasis in lung adenocarcinomas (Mansuet-Lupo et al, 2019). A strong interaction between tumor genomics and immunotherapy programs has to be highlighted. D. Damotte and K Leroy established the association of the tumor inflammation signature and clinical benefit of anti-PD1 treatment in a multi-cancer cohort and specifically in NSCLC (Damotte J Transl Med. 2019). A program analyzing the different biomarkers (T resident memory cells, gene expression signature, T-cell clonality) associated with ICI sensitivity is coordinated by Pr Eric Tartour, in collaboration with P Laurent-Puig and I Cremer teams (SIGN’IT grant from ARC 2018). In gynaecological cancers, J Alexandre, PA Just, and K Leroy set-up the molecular classification for prognosis of endometrial cancers based on TCGA datasets and reported the low expression of NRF2 target, NQO1 in TP53-mutated tumors (Beinse et al, 2019).
Three research teams have developed a translational research in the field of the genomics of hematological malignancies.
V Asnafi & E Macintyre (INEM) research team essentially involves analysis of the mechanisms controlling human T lymphoid ontogeny and oncogenic transformation in immature T lymphoid malignancies, particularly T-cell lymphoblastic acute leukemias/lymphomas (Trinquand et al Cancer Discovery 2016, Bond et al JCO 2017, Petit et al Blood 2018, Touzart et al CCR 2019). This allowed identification a molecular « classifier » based on mutational status of NOTCH1/FBXW7/RAS/PTEN, which predicts outcome in T-ALL and is currently used in GRAALL2014 trial for T-ALL stratification treatment. These studies are possible due to close collaboration with the adult (GRAALL and LYSA) and pediatric (SFCE Leukemia and Lymphoma committees) clinical cooperative groups, and European networks.
M Fontenay D Bouscary team is involved in the genomic characterization and pronostication of MDS and acute myeloid leukemias based on national cohorts (Bondu et al, 2019) and in the context of international initiatives for prognostication of genetic alterations in myelodysplastic syndromes: IWG-PM (PI: MSKCC, NYC), FP7 TRIAGE (PI Nijmegen, The Netherlands), MDS-RIGHT/H2020 (PI: Nijmegen, The Netherlands) (Haase et al, 2019). This team also participates in the identification of gene signature and genetic biomarkers of response to treatments (Chesnais et al, 2016; Kerdivel et al, 2018; Mondesir et al, 2019; European program HARMONY, PI G Sanz, Spain).
Hermine team has main a translational research program dedicated to the genomic characterization and monitoring of virus-induced lymphoproliferative disorders (Kataoka et al, 2019; Marcais et al, 2016; Artesi et al, 2017; Sarkozy et al, 2017).
These research areas are developed in the program 1 and 2 of the SIRIC CARPEM.
Interactions between medical tumor boards and research team meetings allow bidirectional translational research for care to research and from research to care. Interactions with the SeQOIA platform will facilitate the integration of whole genome, whole exome and RNA-sequencing package to patient care in specific indications including acute lymphoid and myeloid leukemia at high risk of relapse, aggressive lymphomas and patients with solid tumor of less than 40 years old in therapeutic failure. The Paris Cancer Institute: CARPEM will help the translation of discoveries to the clinics and reinforce the integration of immune microenvironment analyses into composite biomarkers for the diagnosis, prognosis and prediction of response to treatments.
|Name Surname||Title/Position||Speciality||Research Unit||Resarch Team|
|Jérôme Alexandre||Full Prof Physician||Oncology||UMRS1138 Centre de Recherche des Cordeliers||Personalized MEdicine, Pharmacogenomics, Therapeutic OPtimization (MEPPOT)|
|Vahid Asnafi||Full Prof Biologist||Hematology||UMRS1151 INEM||Normal and pathological lymphoid differentiation|
|Guillaume Assié||Full Prof Physician||Endocrinology||UMR8102 U1016 Institut Cochin||Genomics and signaling of endocrine tumors|
|Jerôme Bertherat||Full Prof Physician||Endocrinology||UMR8102 U1016 Institut Cochin||Genomics and signaling of endocrine tumors|
|Hélène Blons||Full Prof Biologist||Oncology||UMRS1138 Centre de Recherche des Cordeliers||Personalized MEdicine, Pharmacogenomics, Therapeutic OPtimization (MEPPOT)|
|Didier Bouscary||Full Prof Physician||Hematology||UMR8102 U1016 Institut Cochin||Normal and pathological hematopoiesis|
|Julie Bruneau||Associate Prof||Pathology||U1163 Imagine foundation||Physiopathology and treatment of hematological disorders|
|Nelly Burnichon||Associate Prof||Oncology||UMR970 PARCC||Genetics and metabolism of rare cancers|
|Barbara Burroni||Full time physician||Pathology||Cochin hospital||Department of Pathology|
|Nicolas Chapuis||Associate Prof||Hematology||UMR8102 U1016 Institut Cochin||Normal and pathological hematopoiesis|
|Lucile Couronné||Associate Prof||Cytogenetics||U1163 Imagine foundation||Physiopathology and treatment of hematological disorders|
|Diane Damotte||Full Prof||Pathology||UMRS1138 Centre de Recherche des Cordeliers||Inflammation, Complement and Cancer|
|Judith Favier||Scientist||Oncology/Endocrinology||UMR970 PARCC||Genetics and metabolism of rare cancers|
|Michaela Fontenay||Full Prof Biologist||Hematology||UMR8102 U1016 Institut Cochin||Normal and pathological hematopoiesis|
|Laure Gibault||Full time Physician||Pathology||Hôpital Européen Pompidou||Department of Pathology|
|Anne-Paule Gimenez-Roqueplo||Full Prof||Endocrinology||UMR970 PARCC||Genetics and metabolism of rare cancers|
|Olivier Hermine||Full Prof Physician||Hematology||U1163 Imagine foundation||Physiopathology and treatment of hematological disorders|
|Didier Jean||Scientist||Oncology||UMRS 1138||Functional Genomics of Solid Tumors FunGEST|
|Sophie Kaltenbach||Full time Biologist||Cytogenetics||Necker hospital||Laboratory of cytogenetics|
|Olivier Kosmider||Full Prof Biologist||Hematology||UMR8102 U1016 Institut Cochin||Normal and pathological hematopoiesis|
|Pierre Laurent-Puig||Full Prof||Oncology||UMRS1138 Centre de Recherche des Cordeliers||Personalized MEdicine, Pharmacogenomics, Therapeutic OPtimization (MEPPOT)|
|Karen Leroy||Full Prof Biologist||Oncology||UMRS1138 Centre de Recherche des Cordeliers||Inflammation, Complement and Cancer|
|Letourneur Franck||Research engineer||Molecular biology||UMR8102 U1016 Institut Cochin||Genom’IC platform|
|Eric Letouzé||Scientist||Oncology||UMRS1138 Centre de Recherche des Cordeliers||Functional Genomics of Solid Tumors – FunGeST|
|Ludovic Lhermitte||Associate Prof||Hematology||UMRS1151 INEM||Normal and pathological lymphoid differentiation|
|Elizabeth Macintyre||Full Prof Biologist||Hematology||UMRS1151 INEM||Normal and pathological lymphoid differentiation|
|Thierry Molina||Full Prof||Pathology||U1163 Imagine foundation||Physiopathology and treatment of hematological disorders|
|Eric Pasmant||Full Prof Biologist||Oncology||UMR8102 U1016 Institut Cochin||Genomics and epigenetics of rare tumors|
|Beatrice Romagnolo||Scientist||Oncology||UMR8102 U1016 Institut Cochin||Self-renewal and tumorigenesis of instestinal epithelium|
|Felipe Suarez||Full Prof Physician||Hematology||UMRS1163 Imagine foundation||Physiopathology and treatment of hematological disorders|
|Valérie Taly||Scientist||Oncology||UMRS1138 Centre de Recherche des Cordeliers||Personalized MEdicine, Pharmacogenomics, Therapeutic OPtimization (MEPPOT)|
|Benoît Terris||Full Prof||Pathology||UMR8102 U1016 Institut Cochin||Self-renewal and tumorigenesis of instestinal epithelium|
|Michel Vidaud||Full Prof||Oncology||UMR8102 U1016 Institut Cochin||and epigenetics of rare tumors Genomics|
|Lise Willems||Full time Physician||Hematology||UMR8104 U1016||Normal and pathological hematopoiesis|
|Jessica Zucman-Rossi||Full Prof||Oncology||UMRS1138 Centre de Recherche des Cordeliers||Functional Genomics of Solid Tumors FunGEST|
The selected following publications highlighted the strength clinical and translational research developed in genomics of tumors program:
Number of contribution to international’s cohorts
|Title of the project||Type of the call for project||Period: Start andend dates||Research Institution||Coordinator/investigator|
|microRNAs using highthroughput droplet based microfluidics : a non invasive tool for cancer||ITMO cancer||2016-2020||INSERM/APHP||V. Taly|
|Development of new microfluidic platforms to simulate cancer cells evolution: towards new cancer biomarkers discovery||Ligue nationale contre le Cancer(LNCC)||2016-2020||INSERM/APHP||V. Taly|
|HETCOLI||INSERM Plan Cancer||2016-2020||INSERM||J. Zucman-Rossi|
|LNCC Label||Ligue nationale contre le Cancer(LNCC)||2017/01–2022/01||INSERM/APHP||A.P. Gimenez-Roqueplo|
|Development of a novel biomarker of tumour development in SDHB mutated patients using in vivo metabolic tracingIdentification andvalidation of innovative therapeutic targets in acute leukemia||The Paradifference FoundationLigue nationalecontre le cancer(LNCC) label||2017/07–2020/07||INSERM||J. Favier|
|Identification and validation of innovative therapeutic targets in acute leukemia||Ligue nationale contre le Cancer(LNCC)||2017-2020||INSERM/APHP||D. Bouscary|
|TLR7, viruses and lung cancer||INCa||2016.11/2020.10||INSERM||I. Cremer|
|GETUG AFU26||INCa Translational||2017.10/2020.09||INSERM||L. Albiges (coord)C. Sautès-Fridman|
|European Network for the Study of Adrenal tumors||European Community/H2020 program||2015/06-2020/06||G. Assie (partner)|
|Application of omics based strategies for improved diagnosis and treatment o fendocrine hypertension||Horizon 2020 – H2020-PHC-2014ENS@T-HT||2017/07– 2020/07||M.C. Zennaro (partner)|
|Tumor heterogeneity Program||INSERM Plan Cancer||2016-2020||INSERM Plan cancer||J. Zucman-Rossi (coord)/ P.Laurent-Puig(partner)|
|Sponsor Title||Type of the call for project||Period: Start and end dates||Research Institution||Coordinator/investigator|
|Phase II study evaluating the nivoluman with or without the ipilimumab and the inhibitor of tyrosine kinase according to the molecular group in the metastatic renal cancer.||ARTIC||2017.06/2020.05||INSERM||C. Sautès-Fridman|
|A Phase III open label, randomized, multicentre Trial Testing Early vs Late Onset of EPO Alfa Treatment in Lower Risk MDS, NCT03223961||EPO-PRETAR||2018.01/2021.10||CELGENE/ GFM||O Kosmider|
|A Phase Ib/II study of MEK1/2 inhibitor PD-0325901 or MEK-162 with cMET inhibitor PF-02341066 in RASMT and RASWT (with aberrant c-MET) Colorectal Cancer Patients||MERCURIC||2013-12/2020-11||FP7||P Laurent-Puig|
Centre Universitaire des Saints-Pères Etage 4 – Pièce 446B 45 rue des Saints-Pères -75006 Paris
Carina Binet : Secrétaire Général du CARPEM
Tél. : 01 76 53 43 85 – email@example.com
Aurore Hattabi, PhD : Coordinatrice Scientifique du CARPEM
Tél : 01 76 53 43 85 – firstname.lastname@example.org