The role of BCORL1 in hepatoblastoma

Introduction:

Genetically, HB is a very simple tumor with only 3 mutations per tumor and somatic β-catenin mutations representing the only recurrent alteration found so far. Instead, epigenetic alterations might play a role in the development and progression of this pediatric liver tumor.

Methods:

Mutations were detected by exome and Sanger sequencing. BCORL1 knockout cells were obtained by CRISPR-Cas9 technology. Proliferation was analyzed by MTT assay, expression by real-time PCR and RNA-seq, and histone modifications by ChIP-seq. Bioinformatic analysis was done with DNAstar software, DAVID and GSEA.

Results:

Four out of 79 HB harbored mutations in the BCL6 corepressor like 1 (BCORL1) gene. BCORL1 knockout cells showed a 3-dimensional growth pattern with decreased proliferation rates, which was associated with altered expression of genes associated with adhesion and translation and changes of H3K4me3 marks at candidate loci.

Conclusion:

BCORL1 is an important regulator of gene expression and mutated in a subset of HB.