Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine.
Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine.
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DOI：
10.1038/modpathol.2017.104
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Montironi R
中科院分区：
文献类型：
--
作者：
Cheng L;Lopez-Beltran A;Massari F;MacLennan GT;Montironi R
大约一半的晚期（不可切除或转移的）黑色素瘤含有BRAF基因突变，其中V600E是最常见的突变。BRAF和MEK抑制剂的靶向治疗与BRAF v600突变黑色素瘤患者的显著长期治疗获益相关。因此，BRAF突变的分子检测是确定治疗过程的优先事项。使用MEDLINE/PubMed和科学会议数据库进行文献检索，检索词为“BRAF”、“突变”和“癌症/肿瘤”。“这些结果经过筛选，包括专注于确定BRAF突变状态的诊断测试的手稿。确定了许多BRAF检测方法，包括基于DNA的伴随诊断测试和基于DNA和蛋白质的实验室开发测试。在此，我们回顾了每种方法的特点，并强调了在使用前和在解释每位患者的结果时应考虑的优点和缺点。分子谱分析表明，突变负荷随着黑色素瘤的进展而增加，不同黑色素瘤亚型的遗传变化和进化轨迹可能出现独特的模式。BRAF突变状态在原发和转移病变之间的不一致，以及肿瘤内的异质性，是已知的。此外，对BRAF和MEK抑制剂联合治疗的获得性耐药的发展仍然是一个巨大的障碍。因此，肿瘤异质性和获得性耐药的发展对晚期黑色素瘤患者的分子检测和最终治疗具有重要意义。总的来说，这些信息可以帮助社区肿瘤学家更准确和有效地解释诊断测试结果，在最近的数据背景下表征黑色素瘤肿瘤进展。
Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms ‘BRAF,’ ‘mutation,’ and ‘cancer/tumor.’ These results were filtered to include manuscripts that focused on diagnostic tests for determining BRAF mutation status. Numerous BRAF testing methods were identified, including DNA-based companion diagnostic tests and DNA- and protein-based laboratory-developed tests. Herein we review the characteristics of each method and highlight the strengths and weaknesses that should be considered before use and when interpreting results for each patient. Molecular profiling has shown that mutation load increases with melanoma tumor progression and that unique patterns of genetic changes and evolutionary trajectories for different melanoma subtypes can occur. Discordance in the BRAF mutational status between primary and metastatic lesions, as well as intratumoral heterogeneity, is known to occur. Additionally, the development of acquired resistance to combination BRAF and MEK inhibitor therapy is still a formidable obstacle. Therefore, tumor heterogeneity and the development of acquired resistance have important implications for molecular testing and ultimately the treatment of patients with advanced-stage melanoma. Overall, this information may help community oncologists more accurately and effectively interpret results of diagnostic tests within the context of recent data characterizing melanoma tumor progression.
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