Baak J P A, Path F R C, Hermsen M A J A, Meijer G, Schmidt J, Janssen E A M
Department of Pathology, Central Hospital for Rogaland, Box 8001, 4068 Stavanger, Norway.
Eur J Cancer. 2003 Jun;39(9):1199-215. doi: 10.1016/s0959-8049(03)00265-x.
Cancer development is driven by the accumulation of DNA changes in the approximately 40000 chromosomal genes. In solid tumours, chromosomal numerical/structural aberrations are common. DNA repair defects may lead to genome-wide genetic instability, which can drive further cancer progression. The genes code the actual players in the cellular processes, the 100000-10 million proteins, which in (pre)malignant cells can also be altered in a variety of ways. Over the past decade, our knowledge of the human genome and Genomics (the study of the human genome) in (pre)malignancies has increased enormously and Proteomics (the analysis of the protein complement of the genome) has taken off as well. Both will play an increasingly important role. In this article, a short description of the essential molecular biological cell processes is given. Important genomic and proteomic research methods are described and illustrated. Applications are still limited, but the evidence so far is exciting. Will genomics replace classical diagnostic or prognostic procedures? In breast cancers, the gene expression array is stronger than classical criteria, but in endometrial hyperplasia, quantitative morphological features are more cost-effective than genetic testing. It is still too early to make strong statements, the more so because it is expected that genomics and proteomics will expand rapidly. However, it is likely that they will take a central place in the understanding, diagnosis, monitoring and treatment of (pre)cancers of many different sites.
癌症的发展是由大约40000个染色体基因中DNA变化的积累所驱动的。在实体瘤中,染色体数目/结构畸变很常见。DNA修复缺陷可能导致全基因组的遗传不稳定,进而推动癌症的进一步发展。这些基因编码细胞过程中的实际参与者,即10万到1000万种蛋白质,在(癌)前体细胞中这些蛋白质也可能以多种方式发生改变。在过去十年中,我们对人类基因组以及(癌)前病变中的基因组学(对人类基因组的研究)的了解大幅增加,蛋白质组学(对基因组蛋白质组的分析)也蓬勃发展起来。两者都将发挥越来越重要的作用。本文简要描述了基本的分子生物学细胞过程。介绍并举例说明了重要的基因组学和蛋白质组学研究方法。其应用仍然有限,但目前的证据令人兴奋。基因组学会取代传统的诊断或预后程序吗?在乳腺癌中,基因表达阵列比传统标准更具优势,但在子宫内膜增生中,定量形态学特征比基因检测更具成本效益。现在做出肯定的论断还为时过早,尤其是因为预计基因组学和蛋白质组学将迅速发展。然而,它们很可能在多种不同部位(癌)前病变的理解、诊断、监测和治疗中占据核心地位。