Challenges in bioinformatics approaches to tumor mutation burden analysis.
Challenges in bioinformatics approaches to tumor mutation burden analysis.
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DOI：
10.3892/ol.2021.12816
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发表时间：
2021-07
期刊：
影响因子：
2.9
通讯作者：
Normanno N
中科院分区：
文献类型：
--
作者：
Fenizia F;Pasquale R;Abate RE;Lambiase M;Roma C;Bergantino F;Chaudhury R;Hyland F;Allen C;Normanno N
几种免疫检查点抑制剂（ICIs）已被引入临床实践或处于临床实验的后期阶段。人们正在做出广泛的努力，以确定可靠的生物标志物，以选择可能受益于 ICI 治疗的患者。肿瘤突变负荷（TMB）可能是不同肿瘤类型对 ICI 反应的相关生物标志物；然而，其临床应用受到评估所需分析方法的挑战。已经研究了使用靶向下一代测序面板作为标准全外显子组测序方法的替代方法的可能性。然而，在所涵盖的基因、TMB 估计中包含的突变类型、用于数据分析的生物信息学管道以及用于区分高、中或低 TMB 样本的截止值方面，不存在标准化。生物信息学在靶向测序数据分析中发挥着重要作用，其标准化对于在临床实践中提供可靠的测试至关重要。在本研究中，使用用于 TMB 测试的商业面板对培养和福尔马林固定、石蜡包埋的细胞系进行了分析；将结果与文献和公共数据库的数据进行比较，显示出良好的相关性。此外，高肿瘤突变负荷与微卫星不稳定性之间的相关性也得到了证实。使用两种不同的流程进行生物信息学分析，以强调与开发适当的分析工作流程相关的挑战。
Several immune checkpoint inhibitors (ICIs) have already been introduced into clinical practice or are in advanced phases of clinical experimentation. Extensive efforts are being made to identify robust biomarkers to select patients who may benefit from treatment with ICIs. Tumor mutation burden (TMB) may be a relevant biomarker of response to ICIs in different tumor types; however, its clinical use is challenged by the analytical methods required for its evaluation. The possibility of using targeted next-generation sequencing panels has been investigated as an alternative to the standard whole exome sequencing approach. However, no standardization exists in terms of genes covered, types of mutations included in the estimation of TMB, bioinformatics pipelines for data analysis, and cut-offs used to discriminate samples with high, intermediate or low TMB. Bioinformatics serve a relevant role in the analysis of targeted sequencing data and its standardization is essential to deliver a reliable test in clinical practice. In the present study, cultured and formalin-fixed, paraffin-embedded cell lines were analyzed using a commercial panel for TMB testing; the results were compared with data from the literature and public databases, demonstrating a good correlation. Additionally, the correlation between high tumor mutation burden and microsatellite instability was confirmed. The bioinformatics analyses were conducted using two different pipelines to highlight the challenges associated with the development of an appropriate analytical workflow.
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影响因子：
4
作者：
Chaudhary, Ruchi;Quagliata, Luca;Hyland, Fiona
通讯作者：
Hyland, Fiona
影响因子：
20.4
作者：
Chae, Young Kwang;Viveiros, Pedro;Park, Wungki
通讯作者：
Park, Wungki
影响因子：
6.4
作者：
Endris, Volker;Buchhalter, Ivo;Stenzinger, Albrecht
通讯作者：
Stenzinger, Albrecht
IV期或复发性非小细胞肺癌中的一线Nivolumab。
DOI：
10.1056/nejmoa1613493
发表时间：
2017-06-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Carbone DP;Reck M;Paz-Ares L;Creelan B;Horn L;Steins M;Felip E;van den Heuvel MM;Ciuleanu TE;Badin F;Ready N;Hiltermann TJN;Nair S;Juergens R;Peters S;Minenza E;Wrangle JM;Rodriguez-Abreu D;Borghaei H;Blumenschein GR Jr;Villaruz LC;Havel L;Krejci J;Corral Jaime J;Chang H;Geese WJ;Bhagavatheeswaran P;Chen AC;Socinski MA;CheckMate 026 Investigators
通讯作者：
CheckMate 026 Investigators
DOI：
10.1126/science.aar3593
发表时间：
2018-10-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cristescu R;Mogg R;Ayers M;Albright A;Murphy E;Yearley J;Sher X;Liu XQ;Lu H;Nebozhyn M;Zhang C;Lunceford JK;Joe A;Cheng J;Webber AL;Ibrahim N;Plimack ER;Ott PA;Seiwert TY;Ribas A;McClanahan TK;Tomassini JE;Loboda A;Kaufman D
通讯作者：
Kaufman D