Costa José Luis, Meijer Gerrit, Ylstra Bauke, Caldas Carlos
Institute of Molecular Pathology and Immunology of the University of Porto, University of Porto, Porto, Portugal.
Semin Radiat Oncol. 2008 Apr;18(2):98-104. doi: 10.1016/j.semradonc.2007.10.005.
The molecular genetic investigation of cancer is rapidly evolving because of ever-improving technology. Insights into cancer disease mechanisms are being elucidated using new chromosome-based biomarkers. Until recently, diagnostic and prognostic assessment of diseased tissues and tumors relied heavily on histologic indicators that permitted only general classifications into morphologic subtypes and did not take into account the alterations in individual gene expression or copy number. Genomic and expression profiling now allow the simultaneous interrogation of thousands of genes and offer unprecedented opportunities to obtain global molecular signatures of neoplastic cells in patient samples. One limitation of global profiling at the expression level is that acquisition and optimal transport of high-quality RNA is problematic because of its inherent instability in vitro. In contrast, tumor DNA is stable, relatively easy to transport, and can be obtained from archival paraffin tissue blocks. Thus, there is now a tremendous opportunity to globally profile copy number imbalances in tumors using array comparative genomic hybridization (CGH), which can identify at high resolution the presence of genomic copy number changes in constitutional or tumor DNA samples. Array CGH profiling has already allowed a deeper insight into the biology of a variety of tumor types and in the near future will undoubtedly prove to be a key technology leading to better cancer classification, prognosis, and outcome prediction.
由于技术的不断进步，癌症的分子遗传学研究正在迅速发展。利用新的基于染色体的生物标志物，人们对癌症疾病机制的认识正在不断深入。直到最近，对患病组织和肿瘤的诊断和预后评估在很大程度上依赖于组织学指标，这些指标只能将其大致分类为形态学亚型，而没有考虑个体基因表达或拷贝数的改变。基因组和表达谱分析现在允许同时检测数千个基因，并为获取患者样本中肿瘤细胞的全球分子特征提供了前所未有的机会。在表达水平上进行全球分析的一个局限性在于，由于其在体外固有的不稳定性，高质量RNA的获取和最佳运输存在问题。相比之下，肿瘤DNA是稳定的，相对容易运输，并且可以从存档的石蜡组织块中获得。因此，现在有一个巨大的机会，利用阵列比较基因组杂交（CGH）对肿瘤中的拷贝数失衡进行全球分析，该技术可以高分辨率地识别正常或肿瘤DNA样本中基因组拷贝数变化的存在。阵列CGH分析已经使人们对各种肿瘤类型的生物学有了更深入的了解，并且在不久的将来无疑将被证明是一项关键技术，有助于实现更好的癌症分类、预后和结果预测。
