Swiss Nanoscience Institute, Department of Physics, University of Basel , CH-4056 Basel, Switzerland.
Institute of Pathology, University Hospital Basel , CH-4031 Basel, Switzerland.
Nano Lett. 2016 Sep 14;16(9):5373-7. doi: 10.1021/acs.nanolett.6b01513. Epub 2016 Aug 9.
According to the American skin cancer foundation, there are more new cases of skin cancer than the combined incidence of cancers of the breast, prostate, lung, and colon each year, and malignant melanoma represents its deadliest form. About 50% of all cases are characterized by a particular mutation BRAF(V600E) in the BRAF (Rapid Acceleration of Fibrosarcoma gene B) gene. Recently developed highly specific drugs are able to fight BRAF(V600E) mutated tumors but require diagnostic tools for fast and reliable mutation detection to warrant treatment efficiency. We completed a preliminary clinical trial applying cantilever array sensors to demonstrate identification of a BRAF(V600E) single-point mutation using total RNA obtained from biopsies of metastatic melanoma of diverse sources (surgical material either frozen or fixated with formalin and embedded in paraffin). The method is faster than the standard Sanger or pyrosequencing methods and comparably sensitive as next-generation sequencing. Processing time from biopsy to diagnosis is below 1 day and does not require PCR amplification, sequencing, and labels.
根据美国皮肤癌基金会的数据，每年新增皮肤癌病例比乳腺癌、前列腺癌、肺癌和结肠癌的总和还要多，而恶性黑色素瘤则是其最致命的形式。大约 50%的病例都具有 BRAF (Rapid Acceleration of Fibrosarcoma gene B) 基因中 BRAF(V600E)的特定突变。最近开发的高度特异性药物能够对抗 BRAF(V600E)突变肿瘤，但需要快速可靠的突变检测诊断工具来保证治疗效率。我们完成了一项初步的临床试验，应用悬臂式阵列传感器来证明使用来自不同来源（冷冻或福尔马林固定并石蜡包埋的手术材料）的转移性黑色素瘤活检获得的总 RNA 来识别 BRAF(V600E)单点突变。该方法比标准的 Sanger 或焦磷酸测序方法更快，与下一代测序的灵敏度相当。从活检到诊断的处理时间不到 1 天，且不需要 PCR 扩增、测序和标记。
