PDF(Pubmed)
Abstract：
Risk stratification and molecular targeting have been key to increasing cure rates for pediatric cancers in high-income countries. In contrast, precise diagnosis in low-resource settings is hindered by insufficient pathology infrastructure. The Global HOPE program aims to improve outcomes for pediatric cancer in Sub-Saharan Africa (SSA) by building local clinical care and diagnostic capacity. This study aimed to assess the feasibility of implementing molecular assays to improve leukemia diagnoses in SSA. Custom NanoString nCounter gene fusion assays, previously validated in the US, were used to test samples from suspected leukemia patients. The NanoString platform was chosen due to relatively low cost, minimal technical and bioinformatics expertise required, ability to test sub-optimal RNA, and rapid turnaround time. Fusion results were analyzed blindly, then compared to morphology and flow cytometry results. Of 117 leukemia samples, 74 were fusion-positive, 30 were negative, 7 were not interpretable, and 6 failed RNA quality. Nine additional samples were negative for leukemia by flow cytometry and negative for gene fusions. All 74 gene fusions aligned with the immunophenotype determined by flow cytometry. Fourteen samples had additional information available to further confirm the accuracy of the gene fusion results. The testing provided a more precise diagnosis in >60% of cases, and 9 cases were identified that could be treated with an available tyrosine kinase inhibitor, if detected at diagnosis. As risk-stratified and targeted therapies become more available in SSA, implementing this testing in real-time will enable the treatment of pediatric cancer to move toward incorporating risk stratification for optimized therapy.
摘要：
在高收入国家，风险分层和分子靶向是提高儿科癌症治愈率的关键。相比之下,在低资源环境中的精确诊断受到病理基础设施不足的阻碍.全球希望计划旨在通过建立当地的临床护理和诊断能力来改善撒哈拉以南非洲（SSA）儿科癌症的预后。本研究旨在评估在SSA中实施分子检测以改善白血病诊断的可行性。定制NanoStringnCounter基因融合检测，先前在美国验证过，用于检测疑似白血病患者的样本。选择NanoString平台是因为成本相对较低，需要最少的技术和生物信息学专业知识，测试次优RNA的能力，和快速的周转时间。盲目分析融合结果，然后比较形态学和流式细胞术结果。在117个白血病样本中，74为融合阳性，30是阴性的，7不可解释，和6个失败的RNA质量。通过流式细胞术，另外9个样品的白血病阴性，基因融合阴性。所有74个基因融合体与通过流式细胞术确定的免疫表型对齐。十四个样品具有可用于进一步确认基因融合结果的准确性的额外信息。该测试在>60％的病例中提供了更精确的诊断，确定了9例可以用可用的酪氨酸激酶抑制剂治疗的病例，如果在诊断时检测到。随着风险分层和靶向治疗在SSA中变得越来越可用，实时实施这项测试将使儿科癌症的治疗朝着纳入风险分层以优化治疗的方向发展。
