Centre Léon Bérard, Service d'Hématologie Clinique, 69008 Lyon, France.
Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Laboratoire de Biochimie et Biologie moléculaire, 69495 Pierre-Bénite CEDEX, France.
Int J Mol Sci. 2018 Apr 20;19(4):1251. doi: 10.3390/ijms19041251.
High throughput sequencing (HTS) is increasingly important in determining cancer diagnoses, with subsequent prognostic and therapeutic implications. The biology of cancer is becoming increasingly deciphered and it is clear that therapy needs to be individually tailored. Whilst translational research plays an important role in lymphoid malignancies, few guidelines exist to guide biologists and routine laboratories through this constantly evolving field. In this article, we review the challenges of interpreting HTS in lymphoid malignancies and provide a toolkit to interpret single nucleotide variants obtained from HTS. We define the pre-analytical issues such as sequencing DNA obtained from formalin-fixed and paraffin-embedded tissue (FFPE), the acquisition of germline DNA, or the bioinformatic pitfalls, the analytical issues encountered and how to manage them. We describe the main constitutional and cancer databases, their characteristics and limitations, with an emphasis on variant interpretation in lymphoid malignancies. Finally, we discuss the challenges of predictions that one can make using in silico or in vitro modelling, pharmacogenomic screening, and the limits of those prediction tools. This description of the current status in genomic interpretation highlights the need for new large databases and international collaboration in the lymphoma field.
高通量测序（HTS）在确定癌症诊断方面变得越来越重要，具有后续的预后和治疗意义。癌症的生物学正在被越来越多地破译，很明显，治疗需要个体化。虽然转化研究在淋巴恶性肿瘤中发挥着重要作用，但几乎没有指南可以指导生物学家和常规实验室在这个不断发展的领域中前进。在本文中，我们回顾了在解读淋巴恶性肿瘤中的 HTS 时所面临的挑战，并提供了一套工具来解读从 HTS 获得的单核苷酸变异。我们定义了一些分析前的问题，如从福尔马林固定和石蜡包埋组织（FFPE）中获得的测序 DNA，获取胚系 DNA，或生物信息学陷阱，以及分析中遇到的问题和如何管理这些问题。我们描述了主要的遗传性和癌症数据库，及其特征和局限性，重点是在淋巴恶性肿瘤中的变异解读。最后，我们讨论了使用计算机或体外模型进行预测、药物基因组学筛查以及这些预测工具的局限性所带来的挑战。对基因组解读现状的描述突出了淋巴瘤领域需要新的大型数据库和国际合作。
