Shin Su-Jin, Chun Sung-Min, Kim Tae-Im, Kim Yu Jin, Choi Hyun-Jeung, Jang Se Jin, Kim Jihun
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
PLoS One. 2017 May 1;12(5):e0176340. doi: 10.1371/journal.pone.0176340. eCollection 2017.
Mutation analysis of circulating tumor DNA (ctDNA) has recently been introduced as a noninvasive tumor monitoring method. In this study, we tested the mass spectrometric-based MassARRAY platform for multiplexed gene mutation analysis of plasma samples from colorectal cancer (CRC) patients. A total of 160 patients, who underwent curative resection of either primary or metastatic CRC harboring KRAS mutations between 2005 and 2012, were included. Circulating DNA was isolated from plasma was analyzed on the MassARRAY platform with or without selective amplification of mutant DNA fragments. Tumor-specific KRAS mutations were detected in 39.6% (42/106) of patients with distant metastasis, and in 5.6% (3/54) of patients without distant metastasis. Selective amplification of the mutant allele increased sensitivity to 58.5% (62/106) for patients with distant metastasis, and 16.7% (9/54) for patients without distant metastasis. These mutation detection rates were no less than those of droplet digital polymerase chain reaction. Among patients with distant metastasis, detectable plasma KRAS mutations correlated with larger primary tumors and shorter overall survival rate (P = 0.014 and P = 0.003, respectively). In addition, activating PIK3CA mutations were detected together with KRAS mutations in two plasma samples. Taken together, massARRAY platform is a cost-effective, multigene mutation profiling technique for ctDNA with reasonable sensitivity and specificity.
循环肿瘤DNA（ctDNA）的突变分析最近已作为一种非侵入性肿瘤监测方法被引入。在本研究中，我们测试了基于质谱的MassARRAY平台对来自结直肠癌（CRC）患者血浆样本进行多重基因突变分析的能力。纳入了2005年至2012年间接受了原发或转移CRC根治性切除且携带KRAS突变的160例患者。从血浆中分离出循环DNA，在MassARRAY平台上进行分析，对突变DNA片段进行或不进行选择性扩增。在有远处转移的患者中，39.6%（42/106）检测到肿瘤特异性KRAS突变，在无远处转移的患者中，5.6%（3/54）检测到该突变。对突变等位基因进行选择性扩增后，有远处转移患者的灵敏度提高到58.5%（62/106），无远处转移患者的灵敏度提高到16.7%（9/54）。这些突变检测率不低于微滴式数字聚合酶链反应的检测率。在有远处转移的患者中，可检测到的血浆KRAS突变与更大的原发肿瘤和更短的总生存率相关（分别为P = 0.014和P = 0.003）。此外，在两份血浆样本中同时检测到与KRAS突变一起的激活型PIK3CA突变。综上所述，MassARRAY平台是一种用于ctDNA的具有合理灵敏度和特异性的经济高效的多基因突变分析技术。
