title: Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma.
abstract: OBJECTIVE
  Cirrhotic nodules have long been assumed to be the precancerous lesions of hepatocellular carcinoma (HCC). We thus investigated the allelic imbalance (AI) in cirrhotic nodules to define the genetic aberrations in early hepatocarcinogenesis.
  
  
  METHODS
  One hundred eighty cirrhotic nodules from 7 female patients with HCC were collected by microdissection. Their clonality nature was assessed by examining the X chromosome methylation pattern. AI in monoclonal cirrhotic nodules and the corresponding HCCs were analyzed with microsatellite polymorphic markers.
  
  
  RESULTS
  One hundred one out of 180 nodules (56.1%) were monoclonal and the average fractional AI (FAI) was 21%, lower than the 40% in HCC. Their overall AI patterns differed significantly from that in HCC (P < 0.001) with FAI on 2q, 4q, 8p, and Xq higher than the mean value. Comparison of FAI in nodules (stratified by increasing total AI events) further revealed a progressive increase of FAI on 4q, 8p, and Xq. In contrast, FAI on 1p, 13q, 16q, and 17p were low in nodules but rose above the mean only in HCC.
  
  
  CONCLUSIONS
  About half of the cirrhotic nodules are monoclonal and already have chromosome aberrations. AI on 4q, 8p, and Xq may be the earlier mutations, whereas AI on 1p, 13q, 16q, and 17p occurs late in hepatocarcinogenesis.
authors.affiliation: Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: S H
authors.initials: SH
authors.lastname: Yeh
authors.forename: P J
authors.initials: PJ
authors.lastname: Chen
authors.forename: W Y
authors.initials: WY
authors.lastname: Shau
authors.forename: Y W
authors.initials: YW
authors.lastname: Chen
authors.forename: P H
authors.initials: PH
authors.lastname: Lee
authors.forename: J T
authors.initials: JT
authors.lastname: Chen
authors.forename: D S
authors.initials: DS
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D022981:Allelic Imbalance; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged