Identification of RBMS1 in the amplified region 2q24 as a major driver of cellular growth in childhood hepatoblastoma

In the framework of the clinical hepatoblastoma study of the GPOH, we had the opportunity to study samples of 76 hepatoblastoma patients. Using molecular inversion probe (MIP) array technology we generated quantitative chromosomal copy number profiles that uncovered chromosomal alterations, in particular gain of chromosome 2q (44.7%) and in some cases amplification of the region 2q24 (11.8%). This suggests the presence of a so far unidentified oncogene in this chromosomal region. The RBMS1 gene located within the amplicon on chromosome 2q24 encodes a single-stranded DNA/RNA binding protein and showed significant RNA overexpression in 2q24 amplified tumors. This overexpression was validated by immunohistochemical studies at the protein level. RBMS1 knockdown by specific siRNA transfection resulted in a significantly reduced proliferation and marked reduction of the WNT pathway activity in hepatoblastoma cell lines. We identified RBMS1 as a potential oncogenic driver in hepatoblastoma which may exert this function by interaction with the WNT signaling pathway that is pathologically activated in hepatoblastoma.

Publication History

Article published online:
17 May 2022