Utility of the quasi-monomorphic variation range in unresectable metastatic colorectal cancer patients
Utility of the quasi-monomorphic variation range in unresectable metastatic colorectal cancer patients
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DOI：
10.1111/cas.13774
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发表时间：
2018-11-01
期刊：
影响因子：
5.7
通讯作者：
Yoshino, Takayuki
中科院分区：
文献类型：
--
作者：
Bando, Hideaki;Okamoto, Wataru;Yoshino, Takayuki
微卫星不稳定性 (MSI) 状态是抗程序性死亡 1 (PD-1) 抗体治疗的既定预测生物标志物。目前确定肿瘤 MSI 状态的方法需要匹配的正常 DNA。已知一些单核苷酸微卫星标记在白人和亚洲人中几乎没有变异等位基因。因此，这些微卫星制造商的长度几乎被限制在准单态变异范围（QMVR）内。考虑到 MSI 检测在各种类型癌症中的应用，需要一种简单、灵敏且廉价的方法。本研究评估了 QMVR 在确定不可切除的转移性结直肠癌 (mCRC) 患者的 MSI 状态方面的临床效用。该研究招募了 435 名转移性结直肠癌患者。评估了使用肿瘤 DNA 加匹配正常 DNA 的标准方法与仅使用肿瘤 DNA 的测试方法之间 mCRC MSI 状态的一致性。标准方法和测试方法均检测到 11 例 (2.5%) MSI 高病例。检测方法的敏感性和特异性均为100%，表明方法之间完全一致。在单核苷酸标记物中，三名和两名患者的 NR-21 和 BAT-25 分别表现出不一致。正常组织的 MSI 检测结果表明，五名患者中有四名具有 QMVR 之外的罕见种系变异。对于 BAT-26、NR-24 和 MONO-27，所有患者均表现出完全一致性。使用 QMVR，无需匹配的正常 DNA 即可确定 mCRC 的 MSI 状态。
Microsatellite Instability (MSI) status is an established predictive biomarker for the treatment of the anti-programmed death 1 (PD-1) antibody. The current approach to determine the MSI status in tumours requires matched normal DNA. Some mononucleotide microsatellite markers are known to have few variant alleles in both Caucasians and Asians. Therefore, the length of these microsatellite makers is almost confined within the quasi-monomorphic variation range (QMVR). Considering the application of MSI testing for various types of cancers, a simple, sensitive and inexpensive method is desired. This study assessed the clinical utility of the QMVR for determining the MSI status in patients with unresectable metastatic colorectal cancer (mCRC). The study enrolled 435 patients with mCRC. The concordance of the MSI status in mCRC between the standard method using tumour DNA plus matched normal DNA and the testing method using only tumour DNA was evaluated. Eleven (2.5%) MSI-high cases were detected by both the standard and testing methods. The sensitivity and specificity of the testing method were both 100%, indicating complete concordance between the methods. Among the mononucleotide markers, three and two patients showed discordance for NR-21 and BAT-25, respectively. Results from MSI testing with normal tissue indicated that four of five patients had rare germline variants outside the QMVR. For BAT-26, NR-24 and MONO-27, all patients showed complete concordance. Using the QMVR, the MSI status of mCRC can be determined without matched normal DNA.