title: Loss of heterozygosity at D8S262: an early genetic event of hepatocarcinogenesis.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is a multi-factor, multi-step, multi-gene and complicated process resulting from the accumulation of sequential genetic and epigenetic alterations. An important change among them is from precancerous lesions to HCC. However, only few studies have been reported about the sequential genetic changes during hepatocarcinogenesis.
  
  
  METHODS
  We observed firstly molecular karyotypes of 10 matched HCC using Affymetrix single-nucleotide polymorphism (SNP) 6.0 arrays, and found chromosomal fragments with high incidence (more than 70%) of loss of heterozygosity (LOH). Then, we selected 28 microsatellite markers at some gene spanning these chromosomal fragments, and examined the frequency of LOH of 128 matched HCC and 43 matched precancerous lesions-dysplastic nodules (DN) by a PCR-based analysis. Finally, we investigated the expression of proteins encoded by these genes in HCC, DN and the surrounding hepatic tissues.
  
  
  RESULTS
  The result of Affymetrix SNP6.0 arrays demonstrated that more than 70% (7/10) cases had chromosomal fragment deletion on 4q13.3-35.1, 8p23.2-21.2, 16q11.2-24.3, and 17p13.3-12. Among 28 microsatellite markers selected, LOH frequencies at D8S262 for DN and HCC were found to be the highest, 51.2% and 72.7%, respectively. Immunohistochemically, the positive rate of its adjacent gene CSMD1 in HCC, DN, and the surrounding hepatic tissues were 27.3% (35/128), 75% (33/44), and 82% (105/128), respectively.
  
  
  CONCLUSIONS
  LOH at D8S262 may be associated with an early genetic event of hepatocarcinogenesis, and a predictor for the monitor and prevention of HCC.
  The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1557074981159099 .
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China. glzwd16@fmmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Pin
authors.initials: P
authors.lastname: Ren
authors.affiliation: Department of Rehabilitation Medicine, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Wendong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Han
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Zhu
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
authors.forename: Miao
authors.initials: M
authors.lastname: Lan
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China. lyhzhw@fmmu.edu.cn.|Department of Gynaecology and Obstetrics, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China. lyhzhw@fmmu.edu.cn.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, 710038, People's Republic of China. zhwlyh@fmmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D008113:Liver Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins
chemical_list: D014408:Biomarkers, Tumor; C477880:CSMD1 protein, human; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins