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目的:探讨慢性乙型肝炎和肝硬化组织中变异肝细胞结节(NAH)的染色体畸变情况,从分子水平进一步证实其肿瘤性本质.方法:利用激光显微切割技术解剖10个NAH,并提取全基因组DNA,通过基于女性X染色体失活的嵌合性及磷酸苷油酸激酶(PGK)和雄激素受体(AR)基因位点多态性的克隆性分析技术,选择出单克隆性的NAH进行微阵列比较基因组杂交(array-CGH),观察其染色体畸变情况.结果:10个NAH中只有4个为单克隆性增生,可用于进一步分析,且其中一个NAH伴有小细胞改变(SCC).array-CGH分析结果显示,只有伴有SCC的NAH在染色体1q21.2~q25.2,19q13.12~q13.43和8q区域发现有增缢,在染色体4p和8p上有缺失,并且部分与HCC染色体畸变情况一致.而其它3个不伴有SCC的NAH无染色体畸变发生.结论:伴有SCC改变的NAH是一种真性肿瘤,是一种较晚期的癌前病变.
Objective: To investigate the chromosomal aberrations of variant hepatocyte nodules (NAH) in chronic hepatitis B and cirrhosis and to further confirm the nature of tumor from the molecular level.Methods: Ten NAHs were dissected using laser microdissection and extracted Whole genome DNA was cloned by clonal analysis based on chimeric inactivation of female X chromosome and polymorphism of phosphoglycerate oleic acid kinase (PGK) and androgen receptor (AR) gene loci. Monoclonal NAH (Array-CGH) was performed to observe the chromosomal aberrations.Results: Only 4 out of 10 NAH were clonal hyperplasia and could be used for further analysis. One of the NAH was associated with small cell change (SCC) .array-CGH analysis showed that only NAH associated with SCC was found on chromosome 1q21.2 ~ q25.2, 19q13.12 ~ q13.43 and 8q region increased, on chromosome 4p and 8p missing, and part of Which is consistent with the chromosomal aberrations of HCC, while the other three non-chromosomal aberrations of NAH not associated with SCC.Conclusion: NAH with SCC changes is a true tumor, which is a more advanced precancerous lesion.