Kim Jeong Eun, Kim Deokhoon, Hong Yong Sang, Kim Kyu-Pyo, Yoon Young Kwang, Lee Dae Ho, Kim Sang-We, Chun Sung-Min, Jang Se Jin, Kim Tae Won
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul. Korea.
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; Department of Pathology, University of Ulsan college of Medicine, Asan Medical Center, Seoul, Korea.
Transl Oncol. 2018 Apr;11(2):268-274. doi: 10.1016/j.tranon.2018.01.005. Epub 2018 Feb 3.
Pemetrexed and platinum (PP) combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM). However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions). We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR. Interestingly, rare NRAS p.Q61K and EGFR exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in CDKN2A and CDKN2B genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as NRAS and EGFR. No alterations in genes with potential predictive role for PP therapy were found.
培美曲塞与铂类（PP）联合化疗是目前治疗恶性间皮瘤（MM）的标准一线疗法。然而，尚未找到用于PP疗法的有效预测生物标志物。在此，我们对12例接受PP疗法的MM患者进行了靶向外显子组测序，以分析体细胞突变和拷贝数变异。我们在12例患者中鉴定出187个体细胞突变（65个同义突变、102个错义突变、2个无义突变、5个剪接位点突变以及13个小编码插入/缺失）。我们在包括BAP1、TP53、NRAS和EGFR在内的23个基因中鉴定出体细胞突变。有趣的是，在2例患者中观察到罕见的NRAS p.Q61K和EGFR外显子19缺失。我们还发现CDKN2A和CDKN2B基因存在体细胞染色体拷贝数缺失。未发现与PP疗法后反应相关的基因改变。接受PP疗法的MM患者的体细胞突变分析揭示了NRAS和EGFR等潜在治疗靶点的基因改变。未发现对PP疗法具有潜在预测作用的基因改变。
