Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.
Division of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Genome Med. 2019 May 28;11(1):32. doi: 10.1186/s13073-019-0644-8.
Somatic genetic testing is rapidly becoming the standard of care in many adult and pediatric cancers. Previously, the standard approach was single-gene or focused multigene testing, but many centers have moved towards broad-based next-generation sequencing (NGS) panels. Here, we report the laboratory validation and clinical utility of a large cohort of clinical NGS somatic sequencing results in diagnosis, prognosis, and treatment of a wide range of pediatric cancers.
Subjects were accrued retrospectively at a single pediatric quaternary-care hospital. Sequence analyses were performed on 367 pediatric cancer samples using custom-designed NGS panels over a 15-month period. Cases were profiled for mutations, copy number variations, and fusions identified through sequencing, and their clinical impact on diagnosis, prognosis, and therapy was assessed.
NGS panel testing was incorporated meaningfully into clinical care in 88.7% of leukemia/lymphomas, 90.6% of central nervous system (CNS) tumors, and 62.6% of non-CNS solid tumors included in this cohort. A change in diagnosis as a result of testing occurred in 3.3% of cases. Additionally, 19.4% of all patients had variants requiring further evaluation for potential germline alteration.
Use of somatic NGS panel testing resulted in a significant impact on clinical care, including diagnosis, prognosis, and treatment planning in 78.7% of pediatric patients tested in our institution. Somatic NGS tumor testing should be implemented as part of the routine diagnostic workup of newly diagnosed and relapsed pediatric cancer patients.
体细胞基因检测在许多成人和儿科癌症中迅速成为标准治疗方法。以前，标准方法是单基因或重点多基因检测，但许多中心已转向广泛的基于下一代测序（NGS）的面板。在这里，我们报告了大量临床 NGS 体细胞测序结果在诊断、预后和治疗广泛儿科癌症中的实验室验证和临床应用。
在一家儿科四级保健医院回顾性地招募了受试者。在 15 个月的时间内，使用定制设计的 NGS 面板对 367 个儿科癌症样本进行了序列分析。对通过测序鉴定的突变、拷贝数变异和融合进行了案例分析，并评估了其对诊断、预后和治疗的临床影响。
在本队列中包括的白血病/淋巴瘤的 88.7%、中枢神经系统（CNS）肿瘤的 90.6%和非 CNS 实体瘤的 62.6%中，NGS 面板检测被有意义地纳入临床护理。由于检测，诊断发生变化的病例占 3.3%。此外，所有患者中有 19.4%的患者存在需要进一步评估潜在种系改变的变异。
体细胞 NGS 面板检测的使用对临床护理产生了重大影响，包括我们机构检测的 78.7%儿科患者的诊断、预后和治疗计划。体细胞 NGS 肿瘤检测应作为新诊断和复发儿科癌症患者常规诊断工作的一部分实施。
