Mutational signature, cancer driver genes mutations and transcriptomic subgroups predict hepatoblastoma survival.
Eur J Cancer
; 200: 113583, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38330765
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hepatoblastoma
/
Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Child
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article