Kebede Ann M, Garfinkle Elizabeth A R, Mathew Mariam T, Varga Elizabeth, Colace Susan I, Wheeler Gregory, Kelly Benjamin J, Schieffer Kathleen M, Miller Katherine E, Mardis Elaine R, Cottrell Catherine E, Potter Samara L
Division of Pediatric Heme/Onc/BMT, Nationwide Children's Hospital, Columbus, OH, United States.
The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, United States.
Front Oncol. 2024 Dec 2;14:1498409. doi: 10.3389/fonc.2024.1498409. eCollection 2024.
Despite the increasing availability of comprehensive next generation sequencing (NGS), its role in characterizing pediatric hematologic malignancies remains undefined. We describe findings from comprehensive genomic profiling of hematologic malignancies at a pediatric tertiary care center. Patients enrolled on a translational research protocol to aid in cancer diagnosis, prognostication, treatment, and detection of cancer predisposition. Disease-involved samples underwent exome and RNA sequencing and analysis for single nucleotide variation, insertion/deletions, copy number alteration, structural variation, fusions, and gene expression. Twenty-eight patients with hematologic malignancies were nominated between 2018-2021. Eighteen individuals received both germline and somatic sequencing; two received germline sequencing only. Germline testing identified patients with cancer predisposition syndromes and non-cancer carrier states. Fifteen patients (15/18, 83%) had cancer-relevant somatic findings. Potential therapeutic targets were identified in seven patients (7/18, 38.9%); three (3/7, 42.9%) received targeted therapies and remain in remission an average of 47 months later.
尽管全面的下一代测序(NGS)技术越来越容易获得,但其在儿科血液系统恶性肿瘤特征描述中的作用仍不明确。我们描述了一家儿科三级护理中心对血液系统恶性肿瘤进行全面基因组分析的结果。患者参加了一项转化研究方案,以协助癌症诊断、预后评估、治疗以及癌症易感性检测。病变样本进行了外显子组和RNA测序,并分析了单核苷酸变异、插入/缺失、拷贝数改变、结构变异、融合和基因表达。2018年至2021年间,共有28例血液系统恶性肿瘤患者被纳入研究。18例患者同时接受了种系和体细胞测序;2例仅接受了种系测序。种系检测确定了患有癌症易感综合征和非癌症携带者状态的患者。15例患者(15/18,83%)有与癌症相关的体细胞发现。7例患者(7/18,38.9%)确定了潜在的治疗靶点;3例(3/7,42.9%)接受了靶向治疗,平均47个月后仍处于缓解状态。