title: Identification of four distinct regions of allelic imbalances on chromosome 1 by the combined comparative genomic hybridization and microsatellite analysis on hepatocellular carcinoma.
abstract: Frequent chromosome 1 abnormalities detected in human hepatocellular carcinoma have been implicated in early genetic events of liver carcinogenesis. Recurrent loss of 1p with a common deleted region 1p36-p34 has been reported from microsatellite analysis, whereas common gain of the whole chromosome q-arm was described from several comparative genomic hybridization studies. The relationships between copy number changes and allelic status however remains unclear. In this study, we have conducted a simultaneous comparative genomic hybridization and microsatellite analysis study on chromosome 1 in 31 hepatocellular carcinoma cases. Microsatellite analysis revealed frequent loss of heterozygosity on 1p at loci D1S468 (74%), D1S450 (67%), D1S2667 (65%), D1S2697 (75%), D1S199 (52%), and D1S234 (67%) corresponded to the distal 1p36 region and coincided with 12 cases (86%) that presented losses on 1p by comparative genomic hybridization analysis. Although comparative genomic hybridization indicated a common deleted region of 1p36-p35 in the current series, microsatellite analysis has refined the smallest overlapping region (SOR) to 1p36.13-p36.22. Gain of 1q as revealed by comparative genomic hybridization suggested low and high-level gains, and cases that displayed an amplicon below the heterochromatic region 1q21-q25. Common allelic imbalances of polymorphic markers D1S2635 (64%), D1S484 (67%), D1S2878 (65%), D1S196 (70%), D1S249 (64%) D1S2785 (75%), D1S2842 (73%) and D1S2836 (74%) that corresponded to the regions 1q23.1-q24.2, 1q32.1 and 1q43-q44 were detected. Three distinct regions of allelic imbalances were thus suggested on recurring 1q gain found in hepatocellular carcinoma. Furthermore, microsatellite analysis has enabled a mapping of common overrepresented regions and suggested SOR on 1q23.1-q23.3 (D1S2635-D1S2878), 1q25.1-q31.1 (D1S452-D1S238), and 1q43 (D1S2785-D1S2842). Our current study has refined chromosome 1 aberrations in hepatocellular carcinoma to four regions of allelic imbalances. The SORs delineated should provide basis for further molecular investigation in hepatocarcinogenesis on genes residing on these chromosomal regions.
authors.affiliation: Department of Clinical Oncology, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
authors.forename: Thomas H-Y
authors.initials: TH
authors.lastname: Leung
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wong
authors.forename: Paul B-S
authors.initials: PB
authors.lastname: Lai
authors.forename: Andrew
authors.initials: A
authors.lastname: Chan
authors.forename: Ka-Fai
authors.initials: KF
authors.lastname: To
authors.forename: Choong-Tsek
authors.initials: CT
authors.lastname: Liew
authors.forename: Wan-Yee
authors.initials: WY
authors.lastname: Lau
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D022981:Allelic Imbalance; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods*