title: Hepatitis B virus core protein variations differ in tumor and adjacent nontumor tissues from patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  To characterize the mutation pattern of a hepatitis B virus (HBV) core protein (HBcAg) derived from hepatocellular carcinoma (HCC) and adjacent nontumor tissues.
  
  
  METHODS
  HBV core gene fragments (nt. 1901-2365) were amplified from 98 HBV-related HCC tissues and 33 adjacent nontumor tissues. The deduced amino acids (AAs) of the core gene were aligned with the prototype sequences of HBV genotypes B and C.
  
  
  RESULTS
  In total, there were 54 positions that showed polymorphism at the deduced AA level. The mutations were predominantly located in three major (codons 83-87, 95-104 and 130-135) and three minor (codons 21-38, 59-63 and 151-155) mutation-clustering regions (MCRs). The substitution rate in MCRs was significantly higher than in mutation-devoid regions (p < 0.001). The most frequently occurring mutations in rank were codon P130T (38.8%), I97L (37.8%) and S87G (23.5%). In addition, there were 7 patients that showed internal deletions in the middle of HBcAg with sizes ranging from 34 to 59 AAs. Unexpectedly, the core genes isolated from tumor tissues had fewer mutations compared with those isolated from adjacent nontumor tissues from the same patients (p < 0.05).
  
  
  CONCLUSIONS
  Accumulation of naturally occurring mutations in certain restricted segments of HBcAg may be related to the development of HCC.
authors.affiliation: Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Cai
authors.forename: Xin
authors.initials: X
authors.lastname: Bai
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Taoyang
authors.initials: T
authors.lastname: Chen
authors.forename: Jinbing
authors.initials: J
authors.lastname: Wang
authors.forename: Gengsun
authors.initials: G
authors.lastname: Qian
authors.forename: Jianren
authors.initials: J
authors.lastname: Gu
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Tu
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens