多灶性肝细胞癌的克隆起源。

Clonal origin of multifocal hepatocellular carcinoma.

机构信息

Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.

出版信息

Cancer. 2010 Sep 1;116(17):4078-85. doi: 10.1002/cncr.25258.

DOI:10.1002/cncr.25258

PMID:20564142

Abstract

BACKGROUND

Hepatocellular carcinoma is the most common primary tumor of the liver. Patients frequently have multiple histologically similar, but anatomically separate tumors. The clonal origin of multiple hepatocellular carcinomas is uncertain.

METHODS

The authors analyzed 31 tumors from 12 different patients (11 women, 1 man), who had multiple hepatocellular carcinomas involving 1 or both lobes. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue using laser capture microdissection. DNA was analyzed for loss of heterozygosity (LOH), X chromosome inactivation status, and TP53 gene mutations.

RESULTS

Ten (83%) of the 12 patients showed LOH in at least 1 of the analyzed microsatellite markers. Concordant LOH patterns between separate hepatocellular carcinomas in individual patients were seen in 8 (80%) of 10 cases, whereas discordant patterns were seen in 2 (20%) of 10 cases. Five (50%) of 10 informative female patients showed identical nonrandom X chromosome inactivation patterns in multiple tumors; 1 case showed discordant nonrandom X chromosome inactivation pattern. TP53 mutations were identified in 8 (67%) of 12 patients. Tumors in 7 (88%) of these 8 patients showed different point mutations. Three patients (Cases 4, 5, and 10) had tumors with additional TP53 point mutations, indicating additional genetic abnormalities in these tumors.

CONCLUSIONS

The data suggested that the significant proportion of patients with multifocal hepatocellular carcinomas have tumors of common clonal origin.

摘要

背景

肝细胞癌是最常见的原发性肝癌。患者通常有多个人为的、组织学上相似但解剖学上独立的肿瘤。多个肝细胞癌的克隆起源尚不确定。

方法

作者分析了 12 名不同患者（11 名女性，1 名男性）的 31 个肿瘤，这些患者的多个肝细胞癌累及 1 个或 2 个肝叶。使用激光捕获显微切割从福尔马林固定、石蜡包埋的组织中提取基因组 DNA。分析 DNA 杂合性丢失（LOH）、X 染色体失活状态和 TP53 基因突变。

结果

12 名患者中有 10 名（83%）至少在 1 个分析的微卫星标记中显示 LOH。10 例中有 8 例（80%）在单个患者的多个肝细胞癌之间显示出一致的 LOH 模式，而在 2 例（20%）中显示出不一致的 LOH 模式。10 名信息丰富的女性患者中有 5 名（50%）在多个肿瘤中显示出相同的非随机 X 染色体失活模式；1 例显示出不一致的非随机 X 染色体失活模式。在 12 名患者中鉴定出 8 名（67%）的 TP53 突变。在这 8 例患者中的 7 例（88%）肿瘤显示出不同的点突变。3 名患者（病例 4、5 和 10）的肿瘤具有额外的 TP53 点突变，表明这些肿瘤存在额外的遗传异常。