文章目录

整合基因组学在儿童癌症中的临床应用超越了靶向突变

原文发布日期：2022-12-30

英文摘要：

摘要翻译：

原文链接：

文章：

整合基因组学在儿童癌症中的临床应用超越了靶向突变

The clinical utility of integrative genomics in childhood cancer extends beyond targetable mutations

原文发布日期：2022-12-30

英文摘要：

We conducted integrative somatic–germline analyses by deeply sequencing 864 cancer-associated genes, complete genomes and transcriptomes for 300 mostly previously treated children and adolescents/young adults with cancer of poor prognosis or with rare tumors enrolled in the SickKids Cancer Sequencing (KiCS) program. Clinically actionable variants were identified in 56% of patients. Improved diagnostic accuracy led to modified management in a subset. Therapeutically targetable variants (54% of patients) were of unanticipated timing and type, with over 20% derived from the germline. Corroborating mutational signatures (SBS3/BRCAness) in patients with germline homologous recombination defects demonstrates the potential utility of PARP inhibitors. Mutational burden was significantly elevated in 9% of patients. Sequential sampling identified changes in therapeutically targetable drivers in over one-third of patients, suggesting benefit from rebiopsy for genomic analysis at the time of relapse. Comprehensive cancer genomic profiling is useful at multiple points in the care trajectory for children and adolescents/young adults with cancer, supporting its integration into early clinical management.

摘要翻译：

我们通过对864个癌症相关基因进行了深度测序分析，并获取了300名 mostly previously treated儿童和青少年/年轻成年患者的完整基因组和转录组数据。大部分患者患有预后不良的癌症或罕见肿瘤，这些患者参与了 SickKids Cancer Sequencing (KiCS) 项目。在临床意义上具有 actionable的变体中，56%的患者被识别出来。诊断精度的提高导致了一部分患者的管理策略发生改变。治疗目标可及的变体（占患者总数的54%）出现的时间和类型并不常见，超过20%来自germline（基因组）。通过SBS3/BRCAness等突变模式来推断携带者具有靶向治疗潜力。9%的患者的突变负担显著增加。通过逐次采样方法，在1/3以上的患者中识别出治疗目标可及的驱动力变化，这表明在复发时进行基因分析是有益的。全面的癌症基因组定位对儿童和青少年/年轻成年的癌症患者的治疗轨迹中的多个阶段都是有帮助的，有助于将其整合到早期临床管理中。