Clonality of nodular lesions in liver cirrhosis and chromosomal abnormalities in monoclonal nodules of altered hepatocytes

Clonality of nodular lesions in liver cirrhosis and chromosomal abnormalities in monoclonal nodules of altered hepatocytes
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肝硬化结节性病变的克隆性和肝细胞单克隆结节的染色体异常

DOI:
10.1111/j.1365-2559.2010.03523.x
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发表时间:
2010-04-01
期刊:
影响因子:
6.4
通讯作者:
Zhang, Wei
Zhang, Wei
中科院分区:
医学2区
文献类型:
--
作者:
Gong, Li;Li, Yan-Hong;Zhang, Wei

文献摘要

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Clonality of nodular lesions in liver cirrhosis and chromosomal abnormalities in monoclonal nodules of altered hepatocytesAims:To investigate the clonality and chromosome abnormalities of nodules of altered hepatocytes (NAH) in liver cirrhosis and determine whether there is a genetic link between monoclonal NAH and hepatocellular carcinoma (HCC).Methods and results:First, 93 nodules from nine hepatitis B virus (HBV)-related liver cirrhosis patients were dissected by laser microdissection. Next, genomic DNA was extracted, pretreated with Hpa II or Hha I, and amplified via nested polymerase chain reaction for the phosphoglycerate kinase and androgen receptor genes. Finally, the chromosomal aberrations of 12 monoclonal NAH were studied using array-based comparative genomic hybridization (array-CGH). Loss of X chromosomal inactivation mosaicism was demonstrated in three large regenerative nodules and 12 NAH with small cell change (SCC), indicating their neoplastic nature. Among the 60 NAH without SCC, 29 (48.33%) were shown to be monoclonal, whereas four glycogen-storing foci and 14 regenerative nodules were found to be polyclonal. Array-CGH analysis revealed chromosomal abnormalities in one NAH with SCC. Moreover, a part of chromosomal abnormalities in the NAH with SCC coincided with those in HCC.Conclusions:Some (48.33%) NAH in HBV-associated cirrhosis, particularly all those with SCC, are already neoplastic lesions. Occurrence of SCC is a late event during NAH progression, suggesting a premalignant phenotype.