Ilié Marius, Hofman Véronique, Bontoux Christophe, Heeke Simon, Lespinet-Fabre Virginie, Bordone Olivier, Lassalle Sandra, Lalvée Salomé, Tanga Virginie, Allegra Maryline, Salah Myriam, Bohly Doriane, Benzaquen Jonathan, Marquette Charles-Hugo, Long-Mira Elodie, Hofman Paul
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Université Côte d'Azur, 06000 Nice, France.
Biobank-related Hospital (BB-0033-00025), Pasteur Hospital, 06000 Nice, France.
Cancers (Basel). 2022 Apr 30;14(9):2258. doi: 10.3390/cancers14092258.
The number of genomic alterations required for targeted therapy of non-squamous non-small cell lung cancer (NS-NSCLC) patients has increased and become more complex these last few years. These molecular abnormalities lead to treatment that provides improvement in overall survival for certain patients. However, these treated tumors inexorably develop mechanisms of resistance, some of which can be targeted with new therapies. The characterization of the genomic alterations needs to be performed in a short turnaround time (TAT), as indicated by the international guidelines. The origin of the tissue biopsies used for the analyses is diverse, but their size is progressively decreasing due to the development of less invasive methods. In this respect, the pathologists are facing a number of different challenges requiring them to set up efficient molecular technologies while maintaining a strategy that allows rapid diagnosis. We report here our experience concerning the development of an optimal workflow for genomic alteration assessment as reflex testing in routine clinical practice at diagnosis for NS-NSCLC patients by using an ultra-fast-next generation sequencing approach (Ion Torrent Genexus Sequencer, Thermo Fisher Scientific). We show that the molecular targets currently available to personalized medicine in thoracic oncology can be identified using this system in an appropriate TAT, notably when only a small amount of nucleic acids is available. We discuss the new challenges and the perspectives of using such an ultra-fast NGS in daily practice.
在过去几年中,非鳞状非小细胞肺癌(NS-NSCLC)患者靶向治疗所需的基因组改变数量有所增加且变得更加复杂。这些分子异常使得针对某些患者的治疗能够提高总生存率。然而,这些接受治疗的肿瘤不可避免地会产生耐药机制,其中一些耐药机制可用新疗法靶向。正如国际指南所指出的,基因组改变的特征分析需要在短周转时间(TAT)内完成。用于分析的组织活检样本来源多样,但由于侵入性较小的方法不断发展,其样本大小在逐渐减小。在这方面,病理学家面临着许多不同的挑战,要求他们建立高效的分子技术,同时保持能够快速诊断的策略。我们在此报告我们的经验,即通过使用超快速下一代测序方法(赛默飞世尔科技的Ion Torrent Genexus测序仪),开发一种最佳工作流程,用于在NS-NSCLC患者诊断时作为常规临床实践中的反射检测来评估基因组改变。我们表明,使用该系统能够在合适的周转时间内鉴定出目前胸科肿瘤个性化医疗中可用的分子靶点,特别是在仅有少量核酸可用的情况下。我们讨论了在日常实践中使用这种超快速NGS所面临的新挑战和前景。