Tumor mutational burden quantification from targeted gene panels: major advancements and challenges
Tumor mutational burden (TMB), the total number of somatic coding mutations in a tumor, is emerging as a promising biomarker for immunotherapy response in cancer patients. TMB can be quantitated by a number of NGS-based sequencing technologies. Whole Exome Sequencing (WES) allows comprehensive measu...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2019-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/7/1/183.full |
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| author | Sara Gandini Laura Fancello Pier Giuseppe Pelicci Luca Mazzarella |
| author_facet | Sara Gandini Laura Fancello Pier Giuseppe Pelicci Luca Mazzarella |
| author_sort | Sara Gandini |
| collection | DOAJ |
| description | Tumor mutational burden (TMB), the total number of somatic coding mutations in a tumor, is emerging as a promising biomarker for immunotherapy response in cancer patients. TMB can be quantitated by a number of NGS-based sequencing technologies. Whole Exome Sequencing (WES) allows comprehensive measurement of TMB and is considered the gold standard. However, to date WES remains confined to research settings, due to high cost of the large genomic space sequenced. In the clinical setting, instead, targeted enrichment panels (gene panels) of various genomic sizes are emerging as the routine technology for TMB assessment. This stimulated the development of various methods for panel-based TMB quantification, and prompted the multiplication of studies assessing whether TMB can be confidently estimated from the smaller genomic space sampled by gene panels. In this review, we inventory the collection of available gene panels tested for this purpose, illustrating their technical specifications and describing their accuracy and clinical value in TMB assessment. Moreover, we highlight how various experimental, platform-related or methodological variables, as well as bioinformatic pipelines, influence panel-based TMB quantification. The lack of harmonization in panel-based TMB quantification, of adequate methods to convert TMB estimates across different panels and of robust predictive cutoffs, currently represents one of the main limitations to adopt TMB as a biomarker in clinical practice. This overview on the heterogeneous landscape of panel-based TMB quantification aims at providing a context to discuss common standards and illustrates the strong need of further validation and consolidation studies for the clinical interpretation of panel-based TMB values. |
| format | Article |
| id | doaj-art-93f28b8974024c35b0284ef2059935c1 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2019-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-93f28b8974024c35b0284ef2059935c12025-02-04T05:55:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262019-07-017110.1186/s40425-019-0647-4Tumor mutational burden quantification from targeted gene panels: major advancements and challengesSara Gandini0Laura Fancello1Pier Giuseppe Pelicci2Luca Mazzarella3Experimental Oncology, European Institute of Oncology IRCCS, Milan, ItalyAff1 0000 0004 1757 0843grid.15667.33Department of Experimental OncologyIEO, European Institute of Oncology IRCCS Via Adamello 16 20139 Milan ItalyAff1 0000 0004 1757 0843grid.15667.33Department of Experimental OncologyIEO, European Institute of Oncology IRCCS Via Adamello 16 20139 Milan ItalyExperimental Oncology, New Drug Development, European Instititue of Oncology IRCCS, Milan, ItalyTumor mutational burden (TMB), the total number of somatic coding mutations in a tumor, is emerging as a promising biomarker for immunotherapy response in cancer patients. TMB can be quantitated by a number of NGS-based sequencing technologies. Whole Exome Sequencing (WES) allows comprehensive measurement of TMB and is considered the gold standard. However, to date WES remains confined to research settings, due to high cost of the large genomic space sequenced. In the clinical setting, instead, targeted enrichment panels (gene panels) of various genomic sizes are emerging as the routine technology for TMB assessment. This stimulated the development of various methods for panel-based TMB quantification, and prompted the multiplication of studies assessing whether TMB can be confidently estimated from the smaller genomic space sampled by gene panels. In this review, we inventory the collection of available gene panels tested for this purpose, illustrating their technical specifications and describing their accuracy and clinical value in TMB assessment. Moreover, we highlight how various experimental, platform-related or methodological variables, as well as bioinformatic pipelines, influence panel-based TMB quantification. The lack of harmonization in panel-based TMB quantification, of adequate methods to convert TMB estimates across different panels and of robust predictive cutoffs, currently represents one of the main limitations to adopt TMB as a biomarker in clinical practice. This overview on the heterogeneous landscape of panel-based TMB quantification aims at providing a context to discuss common standards and illustrates the strong need of further validation and consolidation studies for the clinical interpretation of panel-based TMB values.https://jitc.bmj.com/content/7/1/183.full |
| spellingShingle | Sara Gandini Laura Fancello Pier Giuseppe Pelicci Luca Mazzarella Tumor mutational burden quantification from targeted gene panels: major advancements and challenges Journal for ImmunoTherapy of Cancer |
| title | Tumor mutational burden quantification from targeted gene panels: major advancements and challenges |
| title_full | Tumor mutational burden quantification from targeted gene panels: major advancements and challenges |
| title_fullStr | Tumor mutational burden quantification from targeted gene panels: major advancements and challenges |
| title_full_unstemmed | Tumor mutational burden quantification from targeted gene panels: major advancements and challenges |
| title_short | Tumor mutational burden quantification from targeted gene panels: major advancements and challenges |
| title_sort | tumor mutational burden quantification from targeted gene panels major advancements and challenges |
| url | https://jitc.bmj.com/content/7/1/183.full |
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