title: Genomic losses at 5q13.2 and 8p23.1 in dysplastic hepatocytes are common events in hepatitis B virus-related hepatocellular carcinoma.
abstract: Chromosomal loci with genomic imbalances are frequently identified in hepatocellular carcinoma (HCC). Greater than two-thirds of hepatitis B virus (HBV)-related HCCs originate from liver cirrhosis following a duration of up to two decades. However, it is unclear whether these genomic imbalances occur and accumulate in dysplastic hepatocytes of the cirrhotic liver during the progression from regenerated nodules to preneoplastic lesions, including dysplastic nodules (DN). In the present study, high-grade DNs (HGDNs) of HBV-related liver cirrhosis were screened to identify loci with genomic imbalances, and the frequency of the identified loci in a group of HCCs was analyzed in order to determine whether there may be a genetic link between liver cirrhosis and HCC. Genomic DNA was extracted from six HGDNs of two cases of HBV-related liver cirrhosis and subjected to array comparative genomic hybridization (CGH) analysis with a NimbleGen 720K microarray. Loci with the most frequently observed genomic imbalances in DNs were further analyzed in 83 cases of HCC by differential polymerase chain reaction (PCR) and quantitative PCR. The array CGH analysis revealed that the majority of genomic imbalances in the HGDNs were genomic losses of small segments, with loss of heterozygosity (LOH) at 5q13.2 and 8p23.1 identified most frequently. Of the 83 HCC cases, 30 (36.1%) cases were identified with LOH at 5q13.2, where known tumor-associated genes are located, including general transcription factor IIH subunit 2 (GTF2H2), baculoviral IAP repeat-containing protein 1 (BIRC1) and occludin (OCLN). LOH frequency at 8p23.1 in HCC was 61.29% (D8S1130) and 68.4% (D8S503) respectively, similar to the results obtained in previous studies. In conclusion, the results of the present study provided evidence that genomic losses at 5q13.2 and 8p23.1 identified in dysplastic hepatocytes of the cirrhotic liver are common events in HCC. HCC-associated chromosomal abnormalities may occur and accumulate in preneoplastic lesions of liver cirrhosis.
authors.affiliation: Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Guang-Yong
authors.initials: GY
authors.lastname: Chen
authors.affiliation: Minimally Invasive Hepatobiliary Cancer Center, Beijing You-An Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Hepatopancreatobiliary and Splenic Medicine, Affiliated Hospital of Medical College of Chinese People's Armed Police Force, Tianjin 300192, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.affiliation: Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China ; Beijing Key Laboratory of Traditional Medicine in Liver Cirrhosis, National Clinical Research Center of Digestive Disease, Beijing 100050, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
keywords: 5q13.2; dysplastic nodule; genomic imbalances; hepatocellular carcinoma; loss of heterozygosity