Wilson Melissa A, Morrissette Jennifer J D, McGettigan Suzanne, Roth David, Elder David, Schuchter Lynn M, Daber Robert D
Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Cancer Genet. 2014 Jun;207(6):272-5. doi: 10.1016/j.cancergen.2014.06.022. Epub 2014 Jun 18.
Testing for somatic mutations in tumor samples is becoming standard practice in a number of tumor types where targeted therapies are available. Since clinical care is dependent on the identification of the presence or absence of specific mutations, it is important that these mutations be identified consistently and accurately. Here we identify in a patient with metastatic melanoma a novel, complex mutation involving BRAF c.1798A>T (p.T599T), c.1799T>A (p.V600E), and c.1803A>T (p.K601N) that was identified by next generation sequencing but not by standard testing methods. The patient was started on a combination therapy inhibiting both BRAF and MEK, and demonstrated a dramatic clinical response. This case highlights the need for improved methods of mutation testing in tumor samples and exposes a pitfall in allele-specific testing methods that can be overcome using next generation sequencing.
在有靶向治疗可用的多种肿瘤类型中，检测肿瘤样本中的体细胞突变正成为标准做法。由于临床治疗依赖于特定突变的有无鉴定，因此一致且准确地鉴定这些突变很重要。在此，我们在一名转移性黑色素瘤患者中鉴定出一种新型复杂突变，该突变涉及BRAF基因的c.1798A>T（p.T599T）、c.1799T>A（p.V600E）和c.1803A>T（p.K601N），此突变通过下一代测序鉴定出来，但未被标准检测方法所识别。该患者开始接受抑制BRAF和MEK的联合治疗，并表现出显著的临床反应。这个病例凸显了改进肿瘤样本突变检测方法的必要性，并揭示了等位基因特异性检测方法中一个可通过下一代测序克服的缺陷。
