DeVita V T, Bleickardt E W
Yale Cancer Center and the Yale University School of Medicine, New Haven, Connecticut 06519, USA.
Cancer J. 2001 Jul-Aug;7 Suppl 1:S2-13.
Despite advances in treatment, long-term outcome of patients with diffuse large B cell lymphoma (DLBCL) is no better today than reported in 1975. A recent study applying DNA microarray technology revealed that patients whose cancer related to patterns of genes expressed in germinal center lymphocytes responded more favorably to chemotherapy than patients whose cancer related to patterns of genes expressed in activated lymphocytes. cDNA and oligonucleotide microarrays are described, and their applications in cancer research are reviewed. In addition to DLBCL, microarray technology has been used to study several types of cancer. The applications of microarray technology are numerous and include profiling gene expression patterns in order to facilitate diagnosis and predict response to therapy; correlating patterns of gene expression with prognosis; and identifying genes and gene products that are associated with tumorigenic phenotype or with drug resistance, among other applications. Microarraytechnology has also been used in cell lines to correlate gene expression and chemotherapy response. Furthermore, microarray technology may provide a useful tool to examine the development of drug resistance in cancer and has recently been used to study changes in gene expression caused by activated c-Myc in primary human fibroblasts. Tissue microarrays are described. In addition to the amplification of limited tissue re sources, tissue microarrays have the advantages of limiting the variability associated with tissue processing and limiting the necessary amount of reagent. Tissue microarrays have been used to determine the frequencies of amplication of 3 major breast cancer genes and identify overexpression of ERBB2 mRNA; assess and compare gene amplification in benign prostatic hyperplasia, primary prostate carcinoma, recurrent prostate tumors, and metastatic tumors; compare aggressiveness of prostate carcinoma in 2 patient populations; and study gene amplification across various tumor types. Furthermore, DNA microarray and tissue microarray techniques can be combined to provide convergent evidence of findings and to examine different aspects of gene expression. DNA array technology may also be used to identify critical molecular targets or to identify the critical rate-limiting step in a cascade of genes under the influence of a mutated gene. The historical progression of goals of the National Cancer Institute is reviewed, as well as the economic impact of reduction in cancer-associated mortality. Future efforts should continue the investment in basic research and more effectively integrate it with clinical trials and with approaches to prevention and treatment.
尽管治疗方法有所进步，但弥漫性大B细胞淋巴瘤（DLBCL）患者的长期预后如今并不比1975年报告的情况更好。最近一项应用DNA微阵列技术的研究表明，癌症与生发中心淋巴细胞中表达的基因模式相关的患者对化疗的反应比癌症与活化淋巴细胞中表达的基因模式相关的患者更有利。文中描述了cDNA和寡核苷酸微阵列，并综述了它们在癌症研究中的应用。除了DLBCL，微阵列技术还被用于研究多种类型的癌症。微阵列技术的应用众多，包括分析基因表达模式以促进诊断和预测治疗反应；将基因表达模式与预后相关联；以及识别与致瘤表型或耐药性相关的基因和基因产物等其他应用。微阵列技术也已用于细胞系，以关联基因表达和化疗反应。此外，微阵列技术可能为研究癌症耐药性的发展提供有用工具，并且最近已用于研究原代人成纤维细胞中活化的c-Myc引起的基因表达变化。文中描述了组织微阵列。除了扩增有限的组织资源外，组织微阵列还具有限制与组织处理相关的变异性以及限制所需试剂量的优点。组织微阵列已用于确定3种主要乳腺癌基因的扩增频率并识别ERBB2 mRNA的过表达；评估和比较良性前列腺增生、原发性前列腺癌、复发性前列腺肿瘤和转移性肿瘤中的基因扩增；比较2个患者群体中前列腺癌的侵袭性；以及研究各种肿瘤类型中的基因扩增。此外，可以将DNA微阵列和组织微阵列技术结合起来提供研究结果的趋同证据，并检查基因表达的不同方面。DNA阵列技术还可用于识别关键分子靶点或识别在突变基因影响下的一系列基因中的关键限速步骤。文中回顾了美国国立癌症研究所目标的历史进展，以及降低癌症相关死亡率的经济影响。未来的努力应继续对基础研究进行投资，并更有效地将其与临床试验以及预防和治疗方法相结合。
