國家衛生研究院 NHRI:Item 3990099045/14298
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/14298


    Title: Open the technical black box of tumor mutational burden (TMB): Factors affecting harmonization and standardization of panel-based TMB
    Authors: Sung, MT;Wang, YH;Li, CF
    Contributors: National Institute of Cancer Research
    Abstract: As tumor mutational burden (TMB) has been approved as a predictive biomarker for immune checkpoint inhibitors (ICIs), next-generation sequencing (NGS) TMB panels are being increasingly used clinically. However, only a few of them have been validated in clinical trials or authorized by administration. The harmonization and standardization of TMB panels are thus essential for clinical implementation. In this review, preanalytic, sequencing, bioinformatics and interpretative factors are summarized to provide a comprehensive picture of how the different factors affect the estimation of panel-based TMB. Among the factors, poor DNA quality, improper formalin fixation and residual germline variants after filtration may overestimate TMB, while low tumor purity may decrease the sensitivity of the TMB panel. In addition, a small panel size leads to more variability when comparing with true TMB values detected by whole-exome sequencing (WES). A panel covering a genomic region of more than 1Mb is more stable for harmonization and standardization. Because the TMB estimate reflects the sum of effects from multiple factors, deliberation based on laboratory and specimen quality, as well as clinical information, is essential for decision making.
    Date: 2022-05-03
    Relation: International Journal of Molecular Sciences. 2022 May 3;23(9):Article number 5097.
    Link to: http://dx.doi.org/10.3390/ijms23095097
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1422-0067&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000794584100001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85129308414
    Appears in Collections:[Others] Periodical Articles

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