title: Mutation Detection of Fibroblast Growth Factor Receptor 3 for Infiltrative Hepatocellular Carcinoma by Whole-Exome Sequencing.
abstract: Gene data on infiltrative hepatocellular carcinoma (iHCC) are still unknown.
  
  
  
  This study aims to identify the gene expression signature of iHCC compared with single nodular (SN)-type HCC according to the gross classification.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.|Department of General Surgery, Huai'an Hospital Affiliated to Xuzhou Medical University, Second People's Hospital of Huai'an City, Huai'an, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Pathology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China.
authors.forename: Luoshun
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Drum Tower Hospital, Medical School of Nanjing University, Zhongshan Road 321, Nanjing, 210008, Jiangsu Province, China. yudongqiu510@163.com.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Qiu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D009154:Mutation; D060888:Real-Time Polymerase Chain Reaction; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: Biomarker; FGFR3; Infiltrative hepatocellular carcinoma; Mutation signatures; Whole-exome sequencing