Hybrid Capture-Based Genomic Profiling Identifies BRAF V600 and Non-V600 Alterations in Melanoma Samples Negative by Prior Testing
Hybrid Capture-Based Genomic Profiling Identifies BRAF V600 and Non-V600 Alterations in Melanoma Samples Negative by Prior Testing
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DOI：
10.1634/theoncologist.2018-0271
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发表时间：
2019-05-01
期刊：
影响因子：
5.8
通讯作者：
Schrock, Alexa B.
中科院分区：
文献类型：
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作者：
Boussemart, Lise;Nelson, Annie;Schrock, Alexa B.
BRAF和MEK抑制剂被批准用于BRAF V600突变的晚期黑色素瘤，缓解率高达70%。对于多种非V600 BRAF改变，也观察到对靶向治疗的反应。因此，灵敏、准确和广泛地检测BRAF改变对于将患者与可用的靶向治疗相匹配至关重要。材料与方法回顾了385例连续的黑色素瘤病例的病理报告，这些病例在临床护理过程中使用基于杂交捕获的下一代测序综合基因组分析（CGP）测定法鉴定出BRAF突变或重排。结果79例（21%）患者既往有BRAF分子检测记录。在BRAF V600突变的病例中，11/57（19%）例有可用数据，既往BRAF检测结果为阴性。在16/20例（80%）非V600突变病例（其中2例携带多种BRAF改变）和2/2例（100%）激活BRAF融合病例中也发现了既往阴性BRAF结果。列出了一个患者子集的临床结局。结论CGP在既往阴性检测的病例中发现了多种激活的BRAF改变。鉴于BRAF/MEK抑制剂在BRAF突变的黑色素瘤中已证实的临床获益，转移性黑色素瘤患者应考虑使用CGP，特别是如果其他检测结果为阴性。
Background BRAF and MEK inhibitors are approved for BRAF V600-mutated advanced melanoma, with response rates of up to 70%. Responses to targeted therapies have also been observed for diverse non-V600 BRAF alterations. Thus, sensitive, accurate, and broad detection of BRAF alterations is critical to match patients with available targeted therapies. Materials and Methods Pathology reports were reviewed for 385 consecutive melanoma cases with BRAF mutations or rearrangements identified using a hybrid capture-based next-generation sequencing comprehensive genomic profiling (CGP) assay during the course of clinical care. Results Records of prior BRAF molecular testing were available for 79 (21%) cases. Of cases with BRAF V600 mutations, 11/57 (19%) with available data were negative by prior BRAF testing. Prior negative BRAF results were also identified in 16/20 (80%) cases with non-V600 mutations, 2 of which harbored multiple BRAF alterations, and in 2/2 (100%) cases with activating BRAF fusions. Clinical outcomes for a subset of patients are presented. Conclusion CGP identifies diverse activating BRAF alterations in a significant fraction of cases with prior negative testing. Given the proven clinical benefit of BRAF/MEK inhibitors in BRAF-mutated melanoma, CGP should be considered for patients with metastatic melanoma, particularly if other testing is negative.