title: Comprehensive allelotyping of well-differentiated human hepatocellular carcinoma with semiquantitative determination of chromosomal gain or loss.
abstract: Allelic imbalance (AI), which represents certain chromosomal gains or losses, has been described in human hepatocellular carcinoma (HCC), but the impact of AI on the early stage of hepatocarcinogenesis has not been fully clarified. Moreover, no previous allelotype studies have identified the difference in chromosomal gain and loss that results in AI. To resolve these problems, we examined 18 well-differentiated HCCs with comprehensive allelotyping by using 400 microsatellite markers with semiquantitative assessment of chromosomal gain or loss. To detect allelic gain effectively, the cutoff value of the allelic imbalance index was set at 0.70. Each allele showing imbalance was subjected to multiplex PCR with use of a retained allele as an internal control to determine whether the imbalance was the result of chromosomal gain or loss. High frequencies of chromosomal gains were detected at 1q (D1S196-D1S2785, 56%), 5q (D5S647-D5S2027, 44%), 6p (6pter-D6S309, 33%), 7 (7pter-D7S657, 22%), and 8q (D8S514-qter, 44%), whereas chromosomal losses were frequently observed at 1p (1pter-D1S234, 22%), 8p (8pter-D8S549, 44%), and 17p (17pter-D17S921, 28%). The extent of overall chromosomal aberration was closely related to the maximum tumor diameter (P = 0.002) and the presence of hepatitis B surface antigen (P = 0.03). Recurrent chromosomal losses at 1p and 8p and gains at 1q and 8q, even in HCCs with a minimal extent of aberrant chromosomes, indicate that these alterations were critical in the early stage of hepatocarcinogenesis. On the other hand, deletions of 13q and 16q were infrequent and were seen only in the most aberrant cases, which suggested that these were late events.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nishimura
authors.forename: Naoshi
authors.initials: N
authors.lastname: Nishida
authors.forename: Teruaki
authors.initials: T
authors.lastname: Itoh
authors.forename: Masato
authors.initials: M
authors.lastname: Kuno
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Minata
authors.forename: Toshiki
authors.initials: T
authors.lastname: Komeda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Iwao
authors.initials: I
authors.lastname: Ikai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000368:Aged; D000483:Alleles; D022981:Allelic Imbalance / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002472:Cell Transformation, Viral / Q000235:genetics; D002872:Chromosome Deletion; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged
chemical_list: D005819:Genetic Markers