Published in:
01-02-2017 | Original Article
Mutation Detection of Fibroblast Growth Factor Receptor 3 for Infiltrative Hepatocellular Carcinoma by Whole-Exome Sequencing
Published in: Digestive Diseases and Sciences | Issue 2/2017
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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.