从肝硬化发展到肝细胞癌过程中的染色体等位基因失衡。

Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma.

作者信息

Yeh S H, Chen P J, Shau W Y, Chen Y W, Lee P H, Chen J T, Chen D S

机构信息

Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.

出版信息

Gastroenterology. 2001 Sep;121(3):699-709. doi: 10.1053/gast.2001.27211.

DOI:10.1053/gast.2001.27211

PMID:11522754

Abstract

BACKGROUND & AIMS: Cirrhotic nodules have long been assumed to be the precancerous lesions of hepatocellular carcinoma (HCC). We thus investigated the allelic imbalance (AI) in cirrhotic nodules to define the genetic aberrations in early hepatocarcinogenesis.

METHODS

One hundred eighty cirrhotic nodules from 7 female patients with HCC were collected by microdissection. Their clonality nature was assessed by examining the X chromosome methylation pattern. AI in monoclonal cirrhotic nodules and the corresponding HCCs were analyzed with microsatellite polymorphic markers.

RESULTS

One hundred one out of 180 nodules (56.1%) were monoclonal and the average fractional AI (FAI) was 21%, lower than the 40% in HCC. Their overall AI patterns differed significantly from that in HCC (P < 0.001) with FAI on 2q, 4q, 8p, and Xq higher than the mean value. Comparison of FAI in nodules (stratified by increasing total AI events) further revealed a progressive increase of FAI on 4q, 8p, and Xq. In contrast, FAI on 1p, 13q, 16q, and 17p were low in nodules but rose above the mean only in HCC.

CONCLUSIONS

About half of the cirrhotic nodules are monoclonal and already have chromosome aberrations. AI on 4q, 8p, and Xq may be the earlier mutations, whereas AI on 1p, 13q, 16q, and 17p occurs late in hepatocarcinogenesis.

摘要

背景与目的

长期以来，肝硬化结节一直被认为是肝细胞癌（HCC）的癌前病变。因此，我们研究了肝硬化结节中的等位基因失衡（AI），以确定肝癌早期发生过程中的基因畸变。

方法

通过显微切割收集了7例女性HCC患者的180个肝硬化结节。通过检查X染色体甲基化模式评估其克隆性。使用微卫星多态性标记分析单克隆肝硬化结节及相应HCC中的AI。

结果

180个结节中有101个（56.1%）为单克隆，平均分数AI（FAI）为21%，低于HCC中的40%。它们的总体AI模式与HCC中的显著不同（P < 0.001），2q、4q、8p和Xq上的FAI高于平均值。对结节中FAI（按总AI事件增加分层）的比较进一步显示，4q、8p和Xq上的FAI逐渐增加。相比之下，1p、13q、16q和17p上的FAI在结节中较低，但仅在HCC中升至平均值以上。