Team 2: Genomics and Biomarkers of Lymphomas and Solid Tumors

Team leader : Fabrice Jardin

Research activities

The “Genomics and Biomarkers of Lymphomas and Solid Tumors” team, hosted at the Henri Becquerel Cancer Center and directed by Pr. Fabrice JARDIN, is actively working on the development and characterization of personalized cancer markers in hematological malignancies and solid tumors.

In partnership with the Biological Resource Center’s (CRB) tumor bank at the Henri Becquerel Center, the team has been developing innovative molecular biology tests and new bioinformatics tools for several years. These efforts have led to publications, patents, and their industrial exploitation under license with the companies Sophia Genetics© and Genexpath©. Examples include the LD-RTPCR LymphoSign® signature, which enables molecular classification of lymphomas by combining targeted transcriptome data and a Random-Forest AI algorithm, and several other tests aimed at identifying fusion transcripts in leukemias, sarcomas, and other tumors.

The team is also heavily involved in the analysis of circulating tumor DNA (ctDNA) in lymphomas using high-throughput sequencing techniques. It contributes to the analysis of biological samples from numerous cohorts in trials promoted by the LYSA cooperative group (SENIOR, GAINED, REMARC, Epi-RCHOP, VALYM), supported by the CALYM Carnot Institute. It is a very active member of the national group FrenchConnect, which aims to standardize and develop ctDNA sequencing activity in lymphomas.

Finally, the team is developing a platform for evaluating immunotherapies and targeted therapies in lymphomas using CAM cell cultures (Chicken Chorioallantoic Membrane). This original approach allows for testing targeted therapies or certain immunotherapies using lymphomatous cell lines or primary cultures. It has already been the subject of several publications by our team or in collaboration and constitutes an alternative and original model compared to murine models or organoids. This model adheres to the 3Rs rule (Reduce, Replace, Refine) that governs laboratory animal experimentation (according to European Directive n°2010/63/EU). This model is currently undergoing validation and is the subject of a related development of ad hoc biological tools (characterization of the immunological response observed on CAM, genetic stability of cells, target editing by CRISPR-Cas9) and bioinformatics tools

Historically, the laboratory was a pioneer in circulating analyses in breast cancers (ESR1 mutation, Sefrioui et al. IJC 2015), colorectal cancers (Sefrioui et al. Br J Cancer 2021), and also ENT cancers. More recently, Dr. Fontanilles developed an application in the field of glioblastoma, highlighting the links between biology, clinical data, and circulating markers (Fontanilles et al. Ann Oncol 2021).

We also apply our expertise to the detection of fusion transcripts in T-cell lymphomas, rare ENT tumors, or bronchial adenocarcinomas (Csanyi-Bastien et al. Am J Surg 2021; Drieux et al. Mol J Diag 2021; Piton et al. Lab Invest 2021).

In terms of collaborations, the team works in connection with the Unicancer Head and Neck federation, GORTEC, ANOCEF clinique, and other translational research teams.

Flagship publications

SELECTED PUBLICATIONS (LYMPHOMA) 2016-2023

• Dubois et al. Biological and Clinical Relevance of Associated Genomic Alterations in MYD88L265P and non-L265P-Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases. CLINICAL CANCER RESEARCH 2017
• Fontanilles et al. Non-invasive detection of somatic mutations using next-generation sequencing in primary central nervous system lymphoma. ONCOTARGET 2017
• Bohers et al. Non-invasive monitoring of diffuse large B-cell lymphoma by cell-free DNA high-throughput targeted sequencing: analysis of a prospective cohort. BLOOD CANCER J. 2018
• Dubois et al. Refining diffuse large B-cell lymphoma subgroups using integrated analysis of molecular profiles. EBIOMEDICINE 2019
• Miloudi et al. XPO1 E571K Mutation Modifies Exportin 1 Localisation and Interactome in B-cell Lymphoma. CANCERS (Basel). 2020
• Bobée et al. Combining gene expression profiling and machine learning to diagnose B-cell non-Hodgkin lymphoma. BLOOD CANCER JOURNAL 2020
• Camus et al. High PDL1/PDL2 gene expression correlates with worse outcome in primary mediastinal large B-cell lymphoma. BLOOD ADV. 2023

SELECTED PUBLICATIONS (SOLID TUMORS) 2020-2023

• Clatot et al. Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer. BREAST CANCER RESEARCH 2020
• Fontanilles et al. Cell-free DNA and circulating TERT promoter mutation for disease monitoring innewly-diagnosed glioblastoma. ACTA NEUROPATHOL COMMUN 2020
• Fontanilles et al. Simultaneous detection of EGFR amplification and EGFRvIII variant using digital PCR-based method in glioblastoma. Acta Neuropathologica Communication. 2020
• Sefrioui et al. CEA, CA19-9, circulating DNA and circulating tumour cell kinetics in patients treated for metastatic colorectal cancer (mCRC), British Journal of Cancer. 2021
• Allouchery V.  Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients. Scientific Reports, 2021.
• Grancher et al. Postoperative circulating tumor DNA detection is associated with the risk of recurrence in patients resected for a stage II colorectal cancer. Frontiers in oncology. 2022
• Fontanilles et al. Usefulness of circulating tumor DNA from cerebrospinal fluid in recurrent high-grade glioma. Revue neurologique. 2022
• Sefrioui et al. Circulating DNA changes are predictive of disease progression after transarterial chemoembolization. International Journal of Cancer, 2022
• Lanic et al. Detection of sarcoma fusions by a next-generation sequencing based-ligation-dependent multiplex RT-PCR assay. M. Mod Pathol. 2022
• Lanic et al. A novel SMARCA2-CREM fusion expending the molecular spectrum of salivary gland hyalinazing clear cell carcinoma beyond the FET genes.  Genes Chromosomes Cancer. 2023
• Lanic et al. Detection of salivary gland and sinonasal fusions by a next-generation sequencing based, ligation-dependent, multiplex RT-PCR assay. Histopathology. 2023
• Drouyer et al. Clinical relevance of circulating ESR1 mutations during endocrine therapy for advanced hormone-dependent endometrial carcinoma. BMC Cancer. 2023
• Noeuveglise et al. Impact of EGFRA289T/V mutation on relapse pattern in glioblastoma. ESMO Open. 2023
• Daban et al. Prognostic value of circulating short-length DNA fragments in unresected glioblastoma patients. Translational oncology. 2024

SELECTED PUBLICATIONS (BIOINFORMATICS) 2020-2023

• Sater et al. UMI-Varcal: A Low-Frequency Variant Caller for UMI-Tagged Paired-End Sequencing Data. Bioinformatics. 2020
• Sater et al. UMI-Gen: A UMI-based read simulator for variant calling evaluation in paired-end sequencing NGS libraries. Comput Struct Biotechnol J. 2020
• Viailly et al. Improving high-resolution copy number variation analysis from next generation sequencing using unique molecular identifiers. BMC Bioinformatics. 2021

Members

Contact

Inserm U1245
Centre Henri Becquerel
Rue d’Amiens
76000 Rouen

Phone: +33 232 08 2451
celine.breton@chb.unicancer.fr
fabrice.jardin@chb.unicancer.fr

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