Poon Terence C W, Wong Nathalie, Lai Paul B S, Rattray Magnus, Johnson Philip J, Sung Joseph J Y
Department of Medicine and Therapeutics, Sir Y. K. Pao Cancer Centre, the Chinese University of Hong Kong, Prince of Wales Hospital, N. T., Hong Kong, The People's Republic of China.
Gastroenterology. 2006 Oct;131(4):1262-70. doi: 10.1053/j.gastro.2006.08.014. Epub 2006 Aug 10.
BACKGROUND & AIMS: It is widely recognized that genomic abnormalities underpin the development of human cancers. Aberrant patterns of chromosomal changes may represent useful information that can be used in classifying the complex traits of liver cancer cases for the genetic events involved in tumor carcinogenesis, tumor progression, and prognosis.
Genome-wide chromosomal aberrations of 158 hepatitis B virus-associated hepatocellular carcinoma (HCC) were studied by comparative genomic hybridization (CGH). By application of a self-organizing tree algorithm, statistically significant CGH events were used to construct an evolutionary tree that could infer patient subgroups with different degrees of tumor progression. The key CGH events in the subgroups were identified. The clinical significance of the groupings and the key CGH events were examined.
Based on the patterns of significant chromosomal aberrations derived, 3 HCC subgroups organized in an evolutionary tree were identified. The groupings possessed information reflecting the degrees of tumor progression, including numbers of chromosomal aberrations, tumor stages, tumor sizes, and disease outcome. Gains of 1q21-23 and 8q22-24 were identified as genomic events associated with the early development of HCC. Gain of 3q22-24, however, was identified as 1 of the late genomic events found to be associated with tumor recurrence and poor overall patient survival.
A tumor progression model for HCC was constructed and revealed chromosomal imbalances that were significantly associated with clinical pathologic characteristics of the disease. This model explains a significant part of the variations in clinical outcome among HCC patients.
人们普遍认识到基因组异常是人类癌症发生发展的基础。染色体变化的异常模式可能代表有用信息，可用于根据肿瘤发生、肿瘤进展和预后所涉及的遗传事件对肝癌病例的复杂特征进行分类。
采用比较基因组杂交（CGH）技术研究了158例乙型肝炎病毒相关性肝细胞癌（HCC）的全基因组染色体畸变情况。通过应用自组织树算法，利用具有统计学意义的CGH事件构建进化树，以推断具有不同肿瘤进展程度的患者亚组。确定了亚组中的关键CGH事件。检验了分组及关键CGH事件的临床意义。
根据得出的显著染色体畸变模式，在进化树中确定了3个HCC亚组。这些分组具有反映肿瘤进展程度的信息，包括染色体畸变数量、肿瘤分期、肿瘤大小和疾病转归。1q21 - 23和8q22 - 24的扩增被确定为与HCC早期发生相关的基因组事件。然而，3q22 - 24的扩增被确定为与肿瘤复发和患者总体生存率差相关的晚期基因组事件之一。
构建了HCC的肿瘤进展模型，揭示了与该疾病临床病理特征显著相关的染色体失衡。该模型解释了HCC患者临床结局差异的很大一部分原因。
