Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Semin Respir Crit Care Med. 2020 Jun;41(3):386-399. doi: 10.1055/s-0039-3399564. Epub 2020 May 25.
Current clinical practice guidelines recognize and as essential molecular biomarkers, and a host of other genetic alterations as emerging biomarkers for non-small cell lung carcinoma patients. The available approaches to detecting relevant alterations in these genes are diverse and often complementary. Laboratories have increasingly migrated away from a "single-gene test" approach, embracing assays that incorporate panels of genes capable of detecting a diverse set of alterations. The adoption of next generation sequencing (NGS) techniques has driven this shift; however, the approach to incorporation of NGS varies greatly between practices. Choice of molecular diagnostics assay, be it single-gene or NGS-based panel, will be driven by cost, urgency, clinical and laboratory focus, and professional considerations. Preanalytic factors including operator expertise, sample type and choice of fixative, and postanalytic factors including informatics pipeline and approaches to variant reporting have a significant impact on the quality of molecular diagnostics results. There is no real "one-size-fits-all" test for genomic profiling for lung cancer; clinicians and laboratorians must be prepared to offer a diverse set of assays in order to address turnaround time requirements and optimize detection of critical but difficult-to-detect tumor alterations such as gene fusions.
目前的临床实践指南认识到和是重要的分子生物标志物，还有许多其他遗传改变是新兴的非小细胞肺癌患者的生物标志物。检测这些基因中相关改变的现有方法多种多样，而且往往是互补的。实验室越来越远离“单基因测试”方法，转而采用包含能够检测多种改变的基因组合的检测方法。下一代测序（NGS）技术的采用推动了这一转变；然而，在实践之间，NGS 的采用方法存在很大差异。分子诊断检测方法的选择，无论是单基因检测还是基于 NGS 的检测面板，将取决于成本、紧迫性、临床和实验室重点以及专业考虑因素。分析前因素，包括操作人员的专业知识、样本类型和固定剂的选择，以及分析后因素，包括信息学管道和变异报告方法，对分子诊断结果的质量有重大影响。对于肺癌的基因组分析，没有真正的“一刀切”的测试；临床医生和实验室人员必须准备提供一系列不同的检测方法，以满足周转时间要求，并优化对关键但难以检测的肿瘤改变的检测，如基因融合。
