title: Copy number gain of granulin-epithelin precursor (GEP) at chromosome 17q21 associates with overexpression in human liver cancer.
abstract: BACKGROUND
  Granulin-epithelin precursor (GEP), a secretory growth factor, demonstrated overexpression in various human cancers, however, mechanism remain elusive. Primary liver cancer, hepatocellular carcinoma (HCC), ranks the second in cancer-related death globally. GEP controlled growth, invasion, metastasis and chemo-resistance in liver cancer. Noted that GEP gene locates at 17q21 and the region has been frequently reported to be amplified in subset of HCC. The study aims to investigate if copy number gain would associate with GEP overexpression.
  
  
  METHODS
  Quantitative Microsatellite Analysis (QuMA) was used to quantify the GEP DNA copy number, and fluorescent in situ hybridization (FISH) was performed to consolidate the amplification status. GEP gene copy number, mRNA expression level and clinico-pathological features were analyzed.
  
  
  RESULTS
  GEP DNA copy number determined by QuMA corroborated well with the FISH data, and the gene copy number correlated with the expression levels (n = 60, r = 0.331, P = 0.010). Gain of GEP copy number was observed in 20% (12/60) HCC and associated with hepatitis B virus infection status (P = 0.015). In HCC with increased GEP copy number, tight association between GEP DNA and mRNA levels were observed (n = 12, r = 0.664, P = 0.019).
  
  
  CONCLUSIONS
  Gain of the GEP gene copy number was observed in 20% HCC and the frequency comparable to literatures reported on the chromosome region 17q. Increased gene copy number contributed to GEP overexpression in subset of HCC.
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China. hermannyung@gmail.com.
authors.forename: Man Kuen
authors.initials: MK
authors.lastname: Yung
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China. kwlo@cuhk.edu.hk.
authors.forename: Kwok Wai
authors.initials: KW
authors.lastname: Lo
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China. wallacey@hku.hk.|Centre for Cancer Research, The University of Hong Kong, Hong Kong, China. wallacey@hku.hk.
authors.forename: Chi Wai
authors.initials: CW
authors.lastname: Yip
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China. gracechung@cuhk.edu.hk.
authors.forename: Grace T Y
authors.initials: GT
authors.lastname: Chung
authors.affiliation: Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China. caroltong@cuhk.edu.hk.
authors.forename: Carol Y K
authors.initials: CY
authors.lastname: Tong
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China. cphyllis@hku.hk.|Centre for Cancer Research, The University of Hong Kong, Hong Kong, China. cphyllis@hku.hk.
authors.forename: Phyllis F Y
authors.initials: PF
authors.lastname: Cheung
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China. tantocheung@hotmail.com.|Department of Surgery, Queen Mary Hospital, Hong Kong, China. tantocheung@hotmail.com.
authors.forename: Tan To
authors.initials: TT
authors.lastname: Cheung
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China. poontp@hku.hk.|Centre for Cancer Research, The University of Hong Kong, Hong Kong, China. poontp@hku.hk.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China. poontp@hku.hk.
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.affiliation: Department of Surgery, Stanford University, Stanford, USA. samso@stanford.edu.
authors.forename: Samuel
authors.initials: S
authors.lastname: So
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China. stfan@hku.hk.|Centre for Cancer Research, The University of Hong Kong, Hong Kong, China. stfan@hku.hk.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China. stfan@hku.hk.
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
authors.affiliation: Department of Surgery, The University of Hong Kong, Hong Kong, China. stcheung@hku.hk.|Centre for Cancer Research, The University of Hong Kong, Hong Kong, China. stcheung@hku.hk.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China. stcheung@hku.hk.|Department of Surgery, The University of Hong Kong, L9-55, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong, China. stcheung@hku.hk.
authors.forename: Siu Tim
authors.initials: ST
authors.lastname: Cheung
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D000077153:Progranulins
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins