Santos Gda C, Zielenska M, Prasad M, Squire J A
Department of Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.
J Clin Pathol. 2007 Jan;60(1):1-7. doi: 10.1136/jcp.2005.034389. Epub 2006 Jun 21.
Chromosomal imbalances represent an important mechanism in cancer progression. A clear association between DNA copy-number aberrations and prognosis has been found in a variety of tumours. Comparative genomic hybridisation studies have detected copy-number increases affecting chromosome 6p in several types of cancer. A systematic analysis of large tumour cohorts is required to identify genomic imbalances of 6p that correlate with a distinct clinical feature of disease progression. Recent findings suggest that a central part of the short arm of chromosome 6p harbours one or more oncogenes directly involved in tumour progression. Gains at 6p have been associated with advanced or metastatic disease, poor prognosis, venous invasion in bladder, colorectal, ovarian and hepatocellular carcinomas. Copy number gains of 6p DNA have been described in a series of patients who presented initially with follicle centre lymphoma, which subsequently transformed to diffuse large B cell lymphoma. Melanoma cytogenetics has consistently identified aberrations of chromosome 6, and a correlation with lower overall survival has been described. Most of the changes observed in tumours to date map to the 6p21-p23 region, which encompasses approximately half of the genes on all of chromosome 6 and one third of the number of CpG islands in this chromosome. Analyses of the genes that cluster to the commonly amplified regions of chromosome 6p have helped to identify a small number of molecular pathways that become deregulated during tumour progression in diverse tumour types. Such pathways offer promise for new treatments in the future.
染色体失衡是癌症进展的重要机制。在多种肿瘤中已发现DNA拷贝数畸变与预后之间存在明确关联。比较基因组杂交研究已在几种癌症中检测到影响6号染色体短臂的拷贝数增加。需要对大型肿瘤队列进行系统分析，以确定与疾病进展的独特临床特征相关的6号染色体短臂基因组失衡。最近的研究结果表明，6号染色体短臂的中心部分含有一个或多个直接参与肿瘤进展的致癌基因。6号染色体短臂的扩增与晚期或转移性疾病、预后不良、膀胱癌、结直肠癌、卵巢癌和肝细胞癌的静脉侵犯有关。在一系列最初表现为滤泡中心淋巴瘤、随后转变为弥漫性大B细胞淋巴瘤的患者中，已描述了6号染色体短臂DNA的拷贝数增加。黑色素瘤细胞遗传学一直发现6号染色体存在畸变，并描述了其与较低总生存率的相关性。迄今为止，在肿瘤中观察到的大多数变化都映射到6p21-p23区域，该区域包含6号染色体上所有基因的约一半以及该染色体上三分之一的CpG岛数量。对聚集在6号染色体短臂常见扩增区域的基因进行分析，有助于识别在不同肿瘤类型的肿瘤进展过程中失调的少数分子途径。这些途径为未来的新治疗方法带来了希望。
