IGF2BP1 Gene Plays Big Role in Neuroblastoma

Neuroblastoma, CT of the abdomen; source: radswiki.net

Expression of the IGF2BP1 gene was associated with more advanced tumors and decreased patient survival in a study of neuroblastoma, suggesting that this could be an oncogene with prognostic value.

In previous work, high expression of the IGF2BP1 protein has been shown to be associated with poor overall prognosis and tumor metastasis in a number of cancers. The protein also appears to sustain elevated MYC expression, and MYCN expression plays a role in neuroblastoma tumorigenesis and tumor type.

“The chromosomal location (17q) of the IGF2BP1 gene, as well as the IGF2BP1 protein-directed enhancement of MYC expression, neural crest cell migration, and cell self-renewal strongly points toward its clinical importance in neuroblastoma,” wrote study author Stefan Hüttelmaier, PhD, of Martin Luther University of Halle-Wittenberg in Halle, Germany, and colleagues.

Investigators tested mRNA expression of IGF2BP family members in two independent microarray data sets. In a separate cohort including 69 neuroblastoma tumors, they also analyzed IGF2BP1 gene copy number, mRNA, and protein abundance. The results were published online ahead of print on March 9 in the Journal of Clinical Oncology.

In the two combined cohorts, they found that 77% to 100% of tumors had substantial IGF2BP1 mRNA levels.

Furthermore, the analysis showed that IGF2BP1 DNA copy numbers were significantly higher in stage IV tumors than in stage I tumors (P < .001). High mRNA expression of IGF2BP1, found in 11 of 88 total tumors tested, was associated with a significantly decreased probability of survival compared with low expression (P < .001). It was also confirmed that IGF2BP1 protein and MYCN mRNA levels were statistically correlated, suggesting that the protein may modulate MYCN levels in this malignancy.

“In neuroblastoma, 17q gain is the most common chromosomal alteration and arguably a powerful predictor factor for patient survival and aggressive disease,” the authors wrote. “We have shown that IGF2BP1 is a new candidate of functional importance within 17q.”

They noted that the IGF2BP1 protein likely has other targets beyond MYC, such as LEF-1 or the LIN28/Let-7 pathway. The researchers concluded that with these results, IGF2BP1 is a gene “of striking importance in neuroblastoma. This gene harbors a clear negative prognostic value at the DNA, mRNA, and protein levels. Moreover, its expression is positively correlated with the most prominent oncogene in neuroblastoma-MYCN.”