Department of Clinical Oncology, The University of Hong Kong, Pokfulam, China.
Acta Pharmacol Sin. 2010 Sep;31(9):1165-71. doi: 10.1038/aps.2010.94. Epub 2010 Aug 2.
Hepatocellular carcinoma (HCC) is among the most lethal of human malignancies. During human multistep hepatocarcinogenesis, genomic gain represents an important mechanism in the activation of proto-oncogenes. In many circumstances, activated oncogenes hold clinical implications both as prognostic markers and targets for cancer therapeutics. Gain of chromosome 1q copy is one of the most frequently detected alterations in HCC and 1q21 is the most frequent minimal amplifying region (MAR). A better understanding of the physiological and pathophysiological roles of target genes within 1q21 amplicon will significantly improve our knowledge in HCC pathogenesis, and may lead to a much more effective management of HCC bearing amplification of 1q21. Such knowledge has long term implications for the development of new therapeutic strategies for HCC treatment. Our research group and others, focused on the identification and characterization of 1q21 target genes such as JTB, CKS1B, and CHD1L in HCC progression. In this review, we will summarize the current scientific knowledge of known target genes within 1q21 amplicon and the precise oncogenic mechanisms of CHD1L will be discussed in detail.
肝细胞癌(HCC)是人类恶性肿瘤中最致命的一种。在人类多步骤肝癌发生过程中,基因组增益是原癌基因激活的重要机制。在许多情况下,激活的癌基因既是预后标志物,也是癌症治疗的靶点,具有临床意义。1q 染色体拷贝数增加是 HCC 中最常检测到的改变之一,1q21 是最常见的最小扩增区域(MAR)。更好地了解 1q21 扩增子内靶基因的生理和病理生理作用,将显著提高我们对 HCC 发病机制的认识,并可能导致对携带 1q21 扩增的 HCC 进行更有效的管理。这种知识对开发 HCC 治疗的新治疗策略具有长期意义。我们的研究小组和其他小组专注于鉴定和表征 HCC 进展中 1q21 上的目标基因,如 JTB、CKS1B 和 CHD1L。在这篇综述中,我们将总结目前关于 1q21 扩增子内已知靶基因的科学知识,并详细讨论 CHD1L 的精确致癌机制。