Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3004-531 Coimbra, Portugal.
iCBR-CIMAGO, Center of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, 3004-531 Coimbra, Portugal.
Int J Mol Sci. 2019 Sep 23;20(19):4711. doi: 10.3390/ijms20194711.
The availability of cytogenetics and cytogenomics technologies improved the detection and identification of tumor molecular signatures as well as the understanding of cancer initiation and progression. The use of large-scale and high-throughput cytogenomics technologies has led to a fast identification of several cancer candidate biomarkers associated with diagnosis, prognosis, and therapeutics. The advent of array comparative genomic hybridization and next-generation sequencing technologies has significantly improved the knowledge about cancer biology, underlining driver genes to guide targeted therapy development, drug-resistance prediction, and pharmacogenetics. However, few of these candidate biomarkers have made the transition to the clinic with a clear benefit for the patients. Technological progress helped to demonstrate that cellular heterogeneity plays a significant role in tumor progression and resistance/sensitivity to cancer therapies, representing the major challenge of precision cancer therapy. A paradigm shift has been introduced in cancer genomics with the recent advent of single-cell sequencing, since it presents a lot of applications with a clear benefit to oncological patients, namely, detection of intra-tumoral heterogeneity, mapping clonal evolution, monitoring the development of therapy resistance, and detection of rare tumor cell populations. It seems now evident that no single biomarker could provide the whole information necessary to early detect and predict the behavior and prognosis of tumors. The promise of precision medicine is based on the molecular profiling of tumors being vital the continuous progress of high-throughput technologies and the multidisciplinary efforts to catalogue chromosomal rearrangements and genomic alterations of human cancers and to do a good interpretation of the relation genotype-phenotype.
细胞遗传学和细胞基因组学技术的出现提高了肿瘤分子特征的检测和鉴定水平，也加深了人们对癌症发生和发展的理解。大规模高通量细胞基因组学技术的应用，快速鉴定出了一些与诊断、预后和治疗相关的癌症候选生物标志物。阵列比较基因组杂交和新一代测序技术的出现，极大地增进了人们对癌症生物学的认识，突出了驱动基因，以指导靶向治疗药物的开发、耐药性预测和药物遗传学。然而，这些候选生物标志物中只有少数几个成功转化为临床应用，为患者带来了明显的获益。技术进步有助于证明细胞异质性在肿瘤进展和对癌症治疗的耐药/敏感性中起着重要作用，这是精准癌症治疗的主要挑战。单细胞测序的出现，在癌症基因组学领域带来了范式转变，因为它有很多应用，对肿瘤患者有明显的益处，即检测肿瘤内异质性、绘制克隆进化图谱、监测治疗耐药性的发展以及检测罕见的肿瘤细胞群。现在似乎很明显，没有一个单一的生物标志物可以提供早期检测和预测肿瘤行为和预后所需的全部信息。精准医学的前景基于对肿瘤的分子谱分析，而高通量技术的持续进步和多学科努力，对人类癌症的染色体重排和基因组改变进行编目，并对基因型-表型的关系进行良好的解释，至关重要。
