East Genomics Laboratory Hub, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Br J Cancer. 2024 Sep;131(5):860-869. doi: 10.1038/s41416-024-02721-8. Epub 2024 Jul 12.
Sarcomas are diverse neoplasms with highly variable histological appearances in which diagnosis is often challenging and management options for metastatic/unresectable disease limited. Many sarcomas have distinctive molecular alterations, but the range of alterations is large, variable in type and rapidly increasing, meaning that testing by limited panels is unable to capture the broad spectrum of clinically pertinent genomic drivers required. Paired whole genome sequencing (WGS) in contrast allows comprehensive assessment of small variants, copy number and structural variants along with mutational signature analysis and germline testing.
Introduction of WGS as a diagnostic standard for all eligible patients with known or suspected soft tissue sarcoma over a 2-year period at a soft tissue sarcoma treatment centre.
WGS resulted in a refinement in the diagnosis in 37% of cases, identification of a target for personalised therapy in 33% of cases, and a germline alteration in 4% of cases.
Introduction of WGS poses logistical and training challenges, but offers significant benefits to this group of patients.
肉瘤是具有高度异质性组织学表现的多种肿瘤，其诊断往往具有挑战性，转移性/不可切除疾病的治疗选择有限。许多肉瘤具有独特的分子改变，但改变的范围很大，类型多样且迅速增加，这意味着通过有限的面板检测无法捕获广泛的临床相关基因组驱动因素。相比之下，配对全基因组测序 (WGS) 可以全面评估小变异、拷贝数和结构变异，以及突变特征分析和种系检测。
在软组织肉瘤治疗中心，将 WGS 作为所有已知或疑似软组织肉瘤患者的诊断标准，在 2 年内引入。
WGS 使 37%的病例的诊断得到了改进，使 33%的病例确定了个性化治疗的靶点，4%的病例确定了种系改变。
WGS 的引入带来了后勤和培训方面的挑战，但为这组患者带来了显著的益处。
