肝细胞癌染色体不稳定性的研究进展

Chromosomal instability of hepatocellular carcinoma

肝细胞癌 (hepatocellularcarcinoma ,HCC)的发展是一个多步过程 ,涉及多染色体的改变 ,且与肿瘤的形态和进展相关。在癌前病变 ,由于DNA甲基化的改变、HBV和HCV的侵入、肿瘤抑制基因的点突变或杂合子丢失 (lossofheterozygosity ,LOH )引起基因表达的改变。肿瘤进展期的特征包括许多染色体上肿瘤抑制基因的LOH。不同的HCC结节所观察到的改变常常是不同的 ,表明其在分子水平上的异质性。这些发现表明HCC的发生过程中遗传学的改变也是一个进行性积累的过程。对HCC分子机制的理解可能获得肿瘤分期的新的标记物 ,评价肿瘤形成的相对危险性 。

The development of hepatocellular carcinoma (HCC) is a multistep process associated with changes in host chromosome, and some of which correlate with the appearance and progression of tumor. Preneoplastic changes in gene expression result from altered DNA methylation, the actions of hepatitis B and C viruses and point mutations or loss of heterozygosity (LOH) in selected by LOH involving tumor suppressor genes on many chromosomes. The change observations in different HCC nodules are often distinct, suggesting heterogeneity on the molecular level. The progressive accumulation of genetic changes in cirrhotic,dysplastic and malignant hepatocellular nodules is in keeping with a multistep process of hepatocarcinogenesis. An understanding of the molecular pathologenesis of HCC may provide new markers for tumor staging,assessment of the relative risk of tumor formation, and open new opportunities for therapeutic intervention.