Integrated genomic analysis identifies driver genes and cisplatin-resistant progenitor phenotype in pediatric liver cancer

IntegraGen is delighted to share this new publication on tumor plasticity and cisplatin resistance in pediatric liver cancers. Sequencing services (WES, RNA-seq, snRNA-seq, RRBS) and expertise support, particularly for single nuclei RNA-seq experiment, were provided by IntegraGen

Background

Hepatoblastoma (HB) is the most frequent type of pediatric liver cancers although it is still considered as a rare tumor. At the molecular level, HB have a simple genetic landscape but a high phenotypic heterogeneity. Current HB treatments are associated to a high survival rate, but some patients develop resistance to chemotherapy with limited other therapeutic alternatives.
This study aimed to understand the molecular drivers of HB plasticity and resistance to chemotherapy, and to suggest alternative therapies.

Results

Through an integrated multi-omic analysis, the authors have updated the genomic landscape of HB by identifying new recurrent drivers and have established a new transcriptomic classification related to cell differentiation and immune infiltration. The multiple sample analyses of pediatric patients revealed a high plasticity of HB cells. This plasticity was confirmed by single nuclei RNAseq experiments. Mutational signatures identified a subgroup of HB cells that are resistant to cisplatine-based chemotherapy and are at the origin of relapses and metastases. These analyses led the team of Jessica Zucman-Rossi to identify biomarkers of interest associated to cisplatin-resistance that are potential targets for new therapeutic strategies.

Conclusion

This integrated genomic analysis revealed the high plasticity of HB cells in relation with resistance to cisplatin and tumor progression. These results enable the identification of drugs targeting progenitor cells to treat children with high risk of resistance.

Click here to read the article.

 

Théo Hirsh

Jessica Zucman