Altered microRNA Expression Patterns in Hepatoblastoma Patients

Altered microRNA Expression Patterns in Hepatoblastoma Patients
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DOI:
10.1593/tlo.09124
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发表时间:
2009-09-01
影响因子:
5
通讯作者:
Taruscio, Domenica
Taruscio, Domenica
中科院分区:
医学3区
文献类型:
--
作者:
Magrelli, Armando;Azzalin, Gianluca;Taruscio, Domenica

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儿童肝癌很少见,仅占恶性肿瘤的1.1%,年发病率为每百万人1.5例。肝母细胞瘤和肝细胞癌是最常见的肝脏恶性肿瘤,发生在15岁或以下的年轻人中。这两种肿瘤的分子基础仍然不清楚,共同的标记物(如CTNNB1、APC、IGF-2)并不总是对散发形式的特征有用;在这方面,最近与癌变有关的microRNA可能在其发病中起关键作用。测序分析CTNNB1和APC,甲基化特异性聚合酶链反应评估IGF-2启动子甲基化状态。采用微阵列和定量逆转录聚合酶链反应检测肝母细胞瘤样品中MicroRNA的表达。虽然在我们的样本中检测到很少的基因组改变,但在肝母细胞瘤中观察到一些microRNA的表达改变。无监督聚类表明,microRNA谱可以区分肿瘤和非肿瘤组织。进一步分析肝母细胞瘤与肝细胞癌的microRNA含量,发现有四种microRNA (miR-214, miR-199a, miR-150)表达上调
Liver cancers in children are rare representing only 1.1% of malignancies, with an annual incidence rate of 1.5 cases per million. Hepatoblastoma and hepatocellular carcinomas are the most common malignancies of the liver occurring in young people aged 15 years or younger. Molecular basis of both tumors are still unclear, and common markers (i. e., CTNNB1, APC, IGF-2) are not always useful in the characterization of sporadic forms; in this respect, microRNA recently associated with carcinogenesis could play a pivotal role in their onset. CTNNB1 and APC were analyzed by sequencing, and IGF-2 promoter methylation status was assessed by methylation-specific polymerase chain reaction. MicroRNA expression was assayed by microarray and quantitative reverse transcription-polymerase chain reaction in hepatoblastoma samples. Although few genomic alterations were detected in ours samples, an altered expression of some microRNA in hepatoblastoma was observed. Unsupervised clustering shows that microRNA profile can distinguish tumor from nontumor tissues. Further analyses of microRNA contents in hepatoblastoma compared with hepatocellular carcinoma highlighted four upregulated microRNA (miR-214, miR-199a, miR-150 [P