Analyzing microsatellite instability and gene mutation in circulating cell-free DNA to monitor colorectal cancer progression.
Analyzing microsatellite instability and gene mutation in circulating cell-free DNA to monitor colorectal cancer progression.
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分析循环游离 DNA 中的微卫星不稳定性和基因突变以监测结直肠癌进展
DOI：
10.21037/tcr-20-2762
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发表时间：
2021-06
影响因子：
0.9
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Fu Y;Ye Y;Liu X;Zhu G;Xu Y;Sun J;Wu H;Feng F;Wen Z;Jiang S;Li Y;Zhang Q
结直肠癌（CRC）是全球癌症相关死亡的第二大原因。微卫星不稳定性（MSI）状态和基因突变的检测可能有助于分子靶向治疗。液体活检是近年来发展起来的一种无创性的肿瘤诊断和监测方法。本研究通过分析MSI和基因突变，探讨液体活检的临床应用价值。方法采用下一代测序技术（NGS）对6例结直肠癌患者血浆和配对的原发肿瘤组织（MPTT）中的循环游离DNA（cfDNA）和组织DNA进行MSI和基因突变分析。结果6例患者（男4例，女2例）均为Ⅰ ~ Ⅲ期。采用免疫组化（MMR-IHC）和NGS（MMR-NGS）检测的5个准单态微卫星标记（MSI-NGS）BAT-25、BAT-26、NR 21、NR 24和NR 27以及4个错配修复（MMR）基因（MSH 2、MSH 6、PMS 2、MLH 1）的表达，协同确定MSI状态。NGS和IHC结果的综合分析显示，这些患者的血浆和MPTT样品中MSI的总发生率分别为1/6和2/6。4例患者在血浆和MPTT中均被定义为微卫星稳定（MSS）。在上述6名患者中，cfDNA中的MSI-NGS检测准确识别了1/2的组织高水平微卫星不稳定性（MSI-H）和4/4的组织MSS，总体准确度为5/6。通过NGS分析这些CRC患者的血浆和MPTT样品中的基因突变谱。在2/6的血浆和4/4的MPTT样品中检测到肿瘤特异性基因突变。两个突变阳性血浆样本来自IIb期和IIIc期CRC患者。结论MSI和基因突变分析是揭示大肠癌分子生物学特征的一种无创性辅助手段。
Background Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Detection of microsatellite instability (MSI) status and gene mutations may be useful for molecular targeted therapy. The liquid biopsy is a newly developed, non-invasive method for tumor diagnosis and monitoring. In this study, we evaluated the possible clinical value of liquid biopsy by analyzing MSI and gene mutation. Methods Next-generation sequencing (NGS) was used to analyze MSI and gene mutation in circulating cell-free DNA (cfDNA) and tissue DNA extracted from 6 CRC patients’ plasma and matched primary tumor tissue (MPTT) samples, respectively. Results A total of 6 patients (4 male, 2 female) were included for analysis, whose stage ranges from stage I through stage III. NGS-based panel of 5 quasi-monomorphic microsatellite markers (MSI-NGS) BAT-25, BAT-26, NR21, NR24 as well as NR27, and 4 mismatch repair (MMR) genes (MSH2, MSH6, PMS2, MLH1) expressions assessed by immunohistochemistry (MMR-IHC) and NGS (MMR-NGS) were used to determine MSI status synergistically. Comprehensive analysis of NGS and IHC results showed that the overall incidences of MSI in plasma and MPTT samples from these patients were 1/6 and 2/6, respectively. 4 patients were defined as microsatellite stable (MSS) in both plasma and MPTT. In the above 6 patients, MSI-NGS detection in cfDNA accurately identified 1/2 of tissue high-level microsatellite instability (MSI-H) and 4/4 of tissue MSS for an overall accuracy of 5/6. Gene mutational profiles in these CRC patients’ plasma and MPTT samples were analyzed by NGS. Tumor-specific gene mutations were detected in 2/6 of plasma and 4/4 of MPTT samples. The two mutation-positive plasma samples were from CRC patients at stage IIb and stage IIIc. Conclusions Analyzing MSI and gene mutation might be a non-invasive supplementary way to reveal the molecular characteristics of CRC.
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DOI：
10.1093/annonc/mdx112
发表时间：
2017-06-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Grasselli J;Elez E;Caratù G;Matito J;Santos C;Macarulla T;Vidal J;Garcia M;Viéitez JM;Paéz D;Falcó E;Lopez Lopez C;Aranda E;Jones F;Sikri V;Nuciforo P;Fasani R;Tabernero J;Montagut C;Azuara D;Dienstmann R;Salazar R;Vivancos A
通讯作者：
Vivancos A
影响因子：
3.7
作者：
Lin, Jen-Kou;Lin, Pei-Ching;Chang, Shih-Ching
通讯作者：
Chang, Shih-Ching
影响因子：
45.3
作者：
Overman, Michael J.;Lonardi, Sara;Andre, Thierry
通讯作者：
Andre, Thierry
DOI：
10.6004/jnccn.2018.0061
发表时间：
2018-07
期刊：
Journal of the National Comprehensive Cancer Network : JNCCN
影响因子：
--
作者：
Benson AB;Venook AP;Al-Hawary MM;Cederquist L;Chen YJ;Ciombor KK;Cohen S;Cooper HS;Deming D;Engstrom PF;Grem JL;Grothey A;Hochster HS;Hoffe S;Hunt S;Kamel A;Kirilcuk N;Krishnamurthi S;Messersmith WA;Meyerhardt J;Mulcahy MF;Murphy JD;Nurkin S;Saltz L;Sharma S;Shibata D;Skibber JM;Sofocleous CT;Stoffel EM;Stotsky-Himelfarb E;Willett CG;Wuthrick E;Gregory KM;Gurski L;Freedman-Cass DA
通讯作者：
Freedman-Cass DA
影响因子：
46.9
作者：
Newman AM;Lovejoy AF;Klass DM;Kurtz DM;Chabon JJ;Scherer F;Stehr H;Liu CL;Bratman SV;Say C;Zhou L;Carter JN;West RB;Sledge GW;Shrager JB;Loo BW Jr;Neal JW;Wakelee HA;Diehn M;Alizadeh AA
通讯作者：
Alizadeh AA