We study 3 types of solid tumors using genomic approaches to better understand their molecular and clinical heterogeneity and develop new diagnostic and prognostic markers. For this we use the last advanced technologies in molecular biology associated to our expertise in bioinformatic.
The various activities of our lab and its members
The FunGeST team at the Cordeliers Research Centre is proud to share that our group leader, Professor Jessica Zucman-Rossi, has been honoured with the 2025 EASL Recognition Award at the annual congress of the European Association for the Study of the Liver (EASL), a leading international event in hepatology.
This prestigious award recognises both the excellence of her scientific contributions and her strong commitment to collaborative, inclusive, and open research.
What I love most in research is the joy of collective discovery. Sometimes, something clicks, and this is a piece of the puzzle that falls into place that makes our understanding grow. When you begin to experience this, you are completely addicted to research. This type of discovery would not be possible without my team.
Warm congratulations to Professor Jessica Zucman-Rossi on this inspiring recognition, which resonates deeply with the entire Cordeliers Research Centre community!
Revealing HPV Insight Using Capture HPV and ViroCapt2 Analysis Within Immuneboost-HPV Cohort (NCT03838263)
Background. Hepatoblastoma is the most frequent pediatric liver cancer. The current treatments lead to 80% of survival rate at 5 years. In this study, we evaluated the clinical relevance of molecular features to identify patients at risk of chemoresistance, relapse and death of disease.
Methods. All the clinical data of 86 children with hepatoblastoma were retrospectively collected. Pathological slides were reviewed, tumor DNA sequencing (by whole exome, whole genome or target) and transcriptomic profiling with RNAseq or 300-genes panel were performed. Associations between the clinical, pathological, mutational and transcriptomic data were investigated.
Results. High-risk patients represented 44% of our series and the median age at diagnosis was 21.9 months (range: 0–208). Alterations of the WNT/ß-catenin pathway and of the 11p15.5 imprinted locus were identified in 98% and 74% of the tumors, respectively. Other cancer driver genes mutations were only found in less than 11% of tumors. After neoadjuvant chemotherapy, disease-specific survival and poor response to neoadjuvant chemotherapy were associated with ‘Liver Progenitor’ (p = 0.00049, p < 0.0001) and ‘Immune Cold’ (p = 0.0011, p < 0.0001) transcriptomic tumor subtypes, SBS35 cisplatin mutational signature (p = 0.018, p = 0.001), mutations in rare cancer driver genes (p = 0.0039, p = 0.0017) and embryonal predominant histological type (p = 0.0013, p = 0.0077), respectively. Integration of the clinical and molecular features revealed a cluster of molecular markers associated with resistance to chemotherapy and survival, enlightening transcriptomic ‘Immune Cold’ and Liver Progenitor’ as a predictor of survival independent of the clinical features.
Conclusions. Response to neoadjuvant chemotherapy and survival in children treated for hepatoblastoma are associated with genomic and pathological features independently of the clinical features.
Hepatoblastomas (HB) display heterogeneous cellular phenotypes that influence the clinical outcome, but the underlying mechanisms are poorly understood. Here, we use a single-cell multiomic strategy to unravel the molecular determinants of this plasticity. We identify a continuum of HB cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activations underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation states. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.
This study is the first GWAS analysis that identified new genetic polymorphisms associated with the risk of hepatocellular carcinoma in European patients with high alcohol intake. It has enlightened the role of the WNT/ß-catenin in the early step of hepatocarcinogenesis. Clinical use to predict the risk of HCC in cirrhotic patients was validated by the team in 2023 (Nahon et al, JHEP, 2023, IF=30).
This is a seminal integrated genomic analysis of pediatric liver tumors that enabled to discover several alterations new cancer driver genes, frequent pre-neoplastic somatic mosaicism in young children with hepatoblastoma, new mechanisms of resistance to cisplatin with the involvement of cell plasticity. These results pave the field of transferring genomic data in clinical practice.
This study highlighted the intra-tumoral molecular heterogeneity at the anatomical level in mesothelioma that must be taken into account for the implementation of precision medicine. It supports the need to analyse multiple tumor samples at distinct anatomical sites in the pleural cavity to guide therapeutic choice.
This publication illustrates our contribution and our exceptional activity in research fields during COVID19 pandemic. Specifically, in this study, the sensitivity of the new SARS-CoV-2 variant Delta to antibody neutralisation was evaluated and proved to be reduced. This particular period has allowed us to establish very fruitful collaborations (Hadjadj J. et al., Science 2020; Planas D. et al, Nat Med 2021; Bruel T. et al.. Nature Med 2021; Planas D. et al. Nature 2022).<br />
This work has demonstrated the power of screening 31 anti-tumor drugs on a large panel of 34 cell lines established from liver cancer patients. Integration with genomic, proteomic and transcriptomic data allowed the identification of new therapeutic targets linked to specific oncogenic alterations. This is seminal work for developing genomics-based precision therapies currently underway by JC Nault in clinical practice.
This study defined histo-molecular gradients that take into account both intra- and inter-tumor heterogeneity and propose a new way of thinking about the pathology of mesothelioma and more generally of cancer. The gradients are strongly associated with prognosis and can guide therapeutic strategies for mesothelioma.
This study is an important improvement of the molecular classification of hepatocellular adenoma we established in 2006 with the discovery of new molecular subtypes and tumor driver genes closely correlated to the clinical features of the patients. Based on this classification JC Nault developed a clinical trial (PHRC funding), and defined the relations with the hormonal context of the patients to refine the prevention of relapses (Demory et al, Hepatology 2022) and with specific phenotypes (Calderaro et al, NEJM 2018).
