Mutation Detection of Fibroblast Growth Factor Receptor 3 for Infiltrative Hepatocellular Carcinoma by Whole-Exome Sequencing

Abstract

Background

Gene data on infiltrative hepatocellular carcinoma (iHCC) are still unknown.

Aims

This study aims to identify the gene expression signature of iHCC compared with single nodular (SN)-type HCC according to the gross classification.

Methods

The whole-exome sequencing was performed in six matched HCC tumor/normal pairs (three infiltrative type and three single nodular type) from six patients who received curative hepatectomy. Subsequent validation using Sanger sequencing and real-time PCR was performed in 30 HCC tumor samples (15 infiltrative type and 15 single nodular type).

Results

Following whole-exome sequencing, Sanger sequencing, and bioinformatics analysis, it revealed significant difference of iHCC from SN-type HCC in gene patterns. Particularly, a typical growth factor receptor tyrosine kinase FGFR3 was predominantly mutated in iHCC. One nonsynonymous variant c.G285T (p.Q95H) and five additional mutations (c.G938A:p.G313D, c.G1291A:p.A431T, c.C1355G:p.T452R, c.C1377T:p.L459L, and c.A1445T:p.E482V) were investigated by whole-exome and Sanger sequencing, respectively. Immunohistochemical studies confirmed the specific expression of FGFR3 in iHCC samples.

Conclusion

Our studies indicated that FGFR3 may be a candidate oncogene in tumor progression and a promising therapeutic target in iHCC patients who had early recurrence.

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