Tumor Mutation Burden as a Cornerstone in Precision Oncology Landscapes: Effect of Panel Size and Uncertainty in Cutoffs

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dc.authoridArga, Kazim Yalcin/0000-0002-6036-1348
dc.contributor.authorBudak, Betul
dc.contributor.authorArga, Kazim Yalcin
dc.date.accessioned2024-07-18T20:45:36Z
dc.date.available2024-07-18T20:45:36Z
dc.date.issued2024
dc.departmentİstanbul Bilgi Üniversitesien_US
dc.description.abstractTumor mutation burden (TMB) has profound implications for personalized cancer therapy, particularly immunotherapy. However, the size of the panel and the cutoff values for an accurate determination of TMB are still controversial. In this study, a pan-cancer analysis was performed on 22 cancer types from The Cancer Genome Atlas. The efficiency of gene panels of different sizes and the effect of cutoff values in accurate TMB determination was assessed on a large cohort using Whole Exome Sequencing data (n = 9929 patients) as the gold standard. Gene panels of four different sizes (i.e., 0.44-2.54 Mb) were selected for comparative analyses. The heterogeneity of TMB within and between cancer types is observed to be very high, and it becomes possible to obtain the exact TMB value as the size of the panel increases. In panels with limited size, it is particularly difficult to recognize patients with low TMB. In addition, the use of a general TMB cutoff can be quite misleading. The optimal cutoff value varies between 5 and 20, depending on the TMB distribution of the different tumor types. The use of comprehensive gene panels and the optimization of TMB cutoff values for different cancer types can make TMB a robust biomarker in precision oncology. Moreover, optimization of TMB can help accelerate translational medicine research, and by extension, delivery of personalized cancer care in the future.en_US
dc.description.sponsorshipMarmara University Scientific Research Projects Committee [FYL-2022-10758]en_US
dc.description.sponsorshipThis work was supported by Marmara University Scientific Research Projects Committee through grant number FYL-2022-10758.en_US
dc.identifier.doi10.1089/omi.2024.0015
dc.identifier.endpage203en_US
dc.identifier.issn1536-2310
dc.identifier.issn1557-8100
dc.identifier.issue4en_US
dc.identifier.pmid38657109en_US
dc.identifier.scopus2-s2.0-85190734684en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage193en_US
dc.identifier.urihttps://doi.org/10.1089/omi.2024.0015
dc.identifier.urihttps://hdl.handle.net/11411/7623
dc.identifier.volume28en_US
dc.identifier.wosWOS:001202593300001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMary Ann Liebert, Incen_US
dc.relation.ispartofOmics-A Journal of Integrative Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectTumor Mutation Burdenen_US
dc.subjectCancer İmmunotherapy Biomarkersen_US
dc.subjectWhole Exome Sequencingen_US
dc.subjectGene Panelen_US
dc.subjectPrecision Medicineen_US
dc.subjectPublic Healthen_US
dc.subjectImmune Checkpoint Inhibitorsen_US
dc.subjectBlockadeen_US
dc.titleTumor Mutation Burden as a Cornerstone in Precision Oncology Landscapes: Effect of Panel Size and Uncertainty in Cutoffs
dc.typeArticle

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