Recurrent genetic alterations in hepatitis C-associated hepatocellular carcinoma detected by genomic microarray: a genetic, clinical and pathological correlation study.
Recurrent genetic alterations in hepatitis C-associated hepatocellular carcinoma detected by genomic microarray: a genetic, clinical and pathological correlation study.
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DOI：
10.1186/s13039-014-0081-8
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发表时间：
2014
影响因子：
1.3
通讯作者：
Yeh MM
中科院分区：
文献类型：
--
作者：
Liu YJ;Zhou Y;Yeh MM
在美国，大约50%的肝细胞癌（HCC）由丙型肝炎病毒（HCV）感染引起。HCV感染诱导肝细胞恶性转化的分子机制仍不清楚。HCC有几种临床和病理分期系统，但没有一种包括生物学参数作为预后的预测指标，也没有一个标准化的HCC分子分类。为了了解hcv相关HCC的潜在致病遗传改变，并有助于HCC的分子分类和患者预后，我们使用来自癌组织和配对附近肝硬化非肿瘤组织的福尔马林固定石蜡包埋（FFPE）标本的DNA全基因组微阵列对HCC的DNA拷贝数改变进行了微阵列分析。我们的研究结果显示，HCC中最常见的染色体畸变（bbbb5 Mb）是染色体增加1q（80%）、8q（60%）、7q（40%）、5p（33%）、7p（33%）、Xq（33%）、5q（27%）和Xp(20%)，以及染色体丢失17p（40%）、4q21.21-q26（33%）、8p（33%）、1p36.11-pter（20%）和9p（20%）。使用STAC算法鉴定出具有统计学意义的较小拷贝数改变（3.9 kb至644 kb），包括FGFR3、RECQL4、NOTCH1、PTEN、TSC2和/或ASPSCR1的丢失以及etv1和/或MAF的增加。遗传数据与病理数据的相关性分析显示，1q21.1-q23.2和8q11.1q13.1的增益与2-4级、中分化或低分化hcc显著相关，5q染色体增益与伴有血管侵袭的hcc显著相关，7q染色体增益与I期hcc显著相关。该研究提供了hcv相关HCC中发生的基因组畸变的详细图谱，并提出了候选基因。此外，对复发异常区域的基因富集分析表明，NF- kappaB和BMP信号通路参与HCC的发生和发展。该研究表明，基因组微阵列测试可用于区分HCC和非肿瘤性肝硬化结节，并通过病理特征的FFPE样本确定与HCC进展相关的预后因素。我们的数据支持基因组微阵列检测在HCC诊断、风险分层和致病研究中的应用。
In the US, approximately 50% of hepatocellular carcinoma (HCC) is caused by hepatitis-C virus (HCV) infection. The molecular mechanism of a malignant transformation of hepatocyte induced by HCV infection is still largely unclear. There are several clinical and pathological staging systems for HCC, but none of them include biological parameters as predictors for prognosis and there has not been a standardized molecular classification of HCC. To understand the underlying pathogenic genetic alterations in HCV-associated HCC and aid in molecular classification of HCC and patient prognosis, microarray analysis of DNA copy number alterations in HCC were conducted using whole genome microarray with DNA from formalin-fixed paraffin-embedded (FFPE) specimens of both cancer tissues and paired nearby cirrhotic non-neoplastic tissues. Our results show that the most common chromosomal aberrations (>5 Mb) observed in HCC were chromosomal gains of 1q (80%), 8q (60%), 7q (40%), 5p (33%), 7p (33%), Xq (33%), 5q (27%), and Xp (20%), as well as chromosome losses of 17p (40%), 4q21.21-q26 (33%), 8p (33%), 1p36.11-pter (20%), and 9p (20%). Statistically significant smaller copy number alterations (3.9 kb to 644 kb) were identified using STAC algorithm, including losses of FGFR3, RECQL4, NOTCH1, PTEN, TSC2, and/or ASPSCR1 and gains of ETV1and/or MAF. Correlation analysis between genetic data and pathological data showed that gain of 1q21.1-q23.2 and gain of 8q11.1q13.1 are significantly associated with grade 2–4 and moderately or poorly differentiated HCCs, and gain of chromosome 5q was significantly associated with HCCs with vascular invasion, while gain of chromosome 7q is significantly associated with stage I HCCs. This study has provided a detailed map of genomic aberrations occurring in HCV-associated HCC and has suggested candidate genes. In addition, gene enrichment analysis on the recurrent abnormal regions indicated NF- kappaB and BMP signaling pathways in HCC development and progression. This study demonstrated that genomic microarray test can be used to distinguish HCC from non- neoplastic cirrhotic nodules and to identify prognostic factors associated with HCC progression using pathologically characterized FFPE samples. Our data support the utility of genomic microarray test for the diagnosis, risk stratification, and pathogenic studies of HCC.
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影响因子：
13.5
作者：
Croquelois, A;Blindenbacher, A;Heim, MH
通讯作者：
Heim, MH
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影响因子：
11.2
作者：
Coulouarn C;Corlu A;Glaise D;Guénon I;Thorgeirsson SS;Clément B
通讯作者：
Clément B
影响因子：
7.5
作者：
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通讯作者：
Sasaki, K
影响因子：
4.2
作者：
Huang, Ka-Te;Huang, Yue-Han;Shan, Yun-Feng
通讯作者：
Shan, Yun-Feng
影响因子：
3.7
作者：
Guo, Xu;Ba, Yanna;Xing, Jinliang
通讯作者：
Xing, Jinliang