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Updated: Jul 11, 2025
Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
Published on: July 22, 2020
Whole-genome sequencing and RNA sequencing analysis reveals novel risk genes and differential expression patterns in
Wuqian Wang1, Na Zhang2, Luan Chen2
1Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; Jiaxing Maternity and Children Health Care Hospital, Affiliated Women and Children Hospital Jiaxing University, Jiaxing, Zhejiang, China.
Insights
Genomic analysis of hepatoblastoma (HB) in children revealed key mutations in CTNNB1, AXIN2, and PARP1, alongside novel potential risk genes like BRCA2 and GPC3. This research advances understanding of pediatric liver cancer mechanisms.
Area of Science:
- Pediatric Oncology
- Cancer Genomics
- Molecular Biology
Background:
- Hepatoblastoma (HB) is a rare pediatric liver cancer with unknown pathogenesis.
- It presents as abdominal lumps and accounts for a significant portion of childhood liver tumors.
Purpose of the Study:
- To identify genetic alterations and gene expression patterns in hepatoblastoma.
- To uncover novel genes and molecular mechanisms driving HB development.
Main Methods:
- Whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) on five HB patient samples.
- Analysis included single nucleotide polymorphisms (SNPs), insertions/deletions (Indels), copy number variations (CNVs), and gene expression profiling.
- Quantitative real-time PCR (qPCR) was used for validation.
Main Results:
- Deleterious mutations were found in CTNNB1, AXIN2, and PARP1.
- Novel candidate genes including BRCA2 and GPC3 were identified.
- Differential expression of IGF1R, METTL1, AXIN2, and TP53 was observed in tumor tissues (P < 0.01).
- The ABCC2 gene was identified as a potential pathogenic risk gene.
Conclusions:
- Genomic and transcriptomic analyses provide insights into HB molecular pathogenesis.
- Identified mutations and differentially expressed genes offer potential targets for diagnosis and therapy.
- Further functional studies are needed for novel candidate genes like BRCA2 and GPC3.
Abstract:
Hepatoblastoma (HB) is an uncommon malignant liver cancer primarily affecting infants and children, characterized by the presence of tissue that resembling fetal hepatocytes, mature liver cells or bile duct cells. The primary symptom in affected children is abdominal lumps. HB constitutes approximately 28% of all liver tumors and two-thirds of liver malignancies in the pediatric and adolescent population. Despite its high prevalence, the underlying mechanism of HB pathogenesis remain largely unknown. To reveal the genetic alternations associated with HB, we conducted a comprehensive genomic study using whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) techniques on five HB patients. We aimed to use WGS to identify somatic variant loci associated with HB, including single nucleotide polymorphisms (SNPs), insertions and deletions (Indels), and copy number variations (CNVs). Notably, we found deleterious mutation in CTNNB1, AXIN2 and PARP1, previously implicated in HB. In addition, we discovered multiple novel genes potentially associated with HB, including BRCA2 and GPC3 which require further functional validation to reveal their contributions to HB development. Furthermore, the American College of Medical Genetics and Genomics (ACMG) analysis identified the ABCC2 gene was the pathogenic gene as a potential risk gene linked with HB. To study the gene expression patterns in HB, we performed RNA-seq analysis and qPCR validation to reveal differential expression of four candidate genes (IGF1R, METTL1, AXIN2 and TP53) in tumors compared to nonneoplastic liver tissue in HB patients (P-Val < 0.01). These findings shed lights on the molecular mechanisms underlying HB development and facilitate to advance future personalized diagnosis and therapeutic interventions of HB.
