Bubendorf L
Institute for Pathology, University of Basel, Switzerland.
Eur Urol. 2001 Aug;40(2):231-8. doi: 10.1159/000049777.
Despite continuous research efforts in the past decades, there are still cancers where no effective treatment is available, such as advanced kidney cancer or hormone-refractory prostate cancer. A better understanding of the molecular mechanisms of cancer development and progression is the basis for the development of new diagnostic and therapeutic strategies. Current developments in genomics have a dramatic impact on the whole field of research. The sequence of the entire human genome will soon be fully sequenced and provide the 'book of life' as a basis for the understanding of human disease.
New technologies have emerged to translate the human genome sequence into gene function and improved diagnostics or treatment modalities. New technologies such as microarrays are not only important for fundamental research, but will also be useful for diagnostic, prognostic or therapeutic purposes in individual patients. DNA microarrays make it possible to analyze the mRNA expression of thousands of genes simultaneously. The resulting comprehensive gene expression surveys lead to the identification of new genes and pathways with importance in cancer development and progression, or as targets for new therapies. The validation and prioritization of genes emerging from genome screening analyses in large series of clinical tumors has become a new bottleneck in research. Therefore, we have recently developed the tissue microarray (TMA) technology to efficiently test the clinical relevance of candidate genes. TMAs are microscope slides containing samples from hundreds of individual tumor specimens. They can be used for large-scale, massively parallel in situ analysis of genetic alterations on a DNA, RNA and protein level using in situ hybridization or immunohistochemistry on hundreds of tumor specimens at a time. Microarray technologies are already increasingly being used in urologic research, and will also have a strong impact on clinical urology.
DNA microarrays and TMAs provide a powerful approach to identify large numbers of new candidate genes, and rapidly validate their clinical impact in large series of human tumors. These technologies will soon lead to a better molecular understanding of urologic tumors, and accelerate the identification of new prognostic markers or therapeutic targets.
尽管在过去几十年中持续进行了研究工作，但仍有一些癌症尚无有效的治疗方法，如晚期肾癌或激素难治性前列腺癌。更好地理解癌症发生和发展的分子机制是开发新的诊断和治疗策略的基础。基因组学的当前发展对整个研究领域产生了巨大影响。整个人类基因组序列即将完全测序，并提供“生命之书”作为理解人类疾病的基础。
已经出现了将人类基因组序列转化为基因功能以及改进诊断或治疗方式的新技术。诸如微阵列等新技术不仅对基础研究很重要，而且对个体患者的诊断、预后或治疗目的也将有用。DNA微阵列使同时分析数千个基因的mRNA表达成为可能。由此产生的全面基因表达调查导致识别出在癌症发生和发展中具有重要意义或作为新疗法靶点的新基因和途径。在大量临床肿瘤中对基因组筛选分析中出现的基因进行验证和排序已成为研究中的一个新瓶颈。因此，我们最近开发了组织微阵列（TMA）技术，以有效测试候选基因的临床相关性。TMA是包含来自数百个个体肿瘤标本的样本的显微镜载玻片。它们可用于在DNA、RNA和蛋白质水平上对数百个肿瘤标本同时进行大规模、大量平行的原位遗传改变分析，使用原位杂交或免疫组织化学。微阵列技术已经越来越多地用于泌尿学研究，并且也将对临床泌尿学产生重大影响。
DNA微阵列和TMA提供了一种强大的方法来识别大量新的候选基因，并迅速在大量人类肿瘤中验证它们的临床影响。这些技术将很快使人们对泌尿肿瘤有更好的分子理解，并加速新的预后标志物或治疗靶点的识别。
