Tumour mutational burden (TMB) has emerged as a promising biomarker to predict immune checkpoint inhibitors (ICIs) response in advanced solid cancers. However, harmonisation of TMB reporting by targeted gene panels is lacking, especially in metastatic tumour samples. To address this issue, we used data of 2841 whole-genome sequenced metastatic cancer biopsies to perform an in silico analysis of TMB determined by seven gene panels (FD1CDx, MSK-IMPACT™, Caris Molecular Intelligence, Tempus xT, Oncomine Tumour Mutation Load, NeoTYPE Discovery Profile and CANCERPLEX) compared to exome-based TMB as a golden standard. Misclassification rates declined from up to 30% to <1% when the cut-point for high TMB was increased. Receiver operating characteristic analysis demonstrated that, for correct classification, the cut-point for each gene panel may vary more than 20%. In conclusion, we here demonstrate that a major limitation for the use of gene panels is inter-assay variation and the need for dynamic thresholds to compare TMB outcomes.
|Number of pages||4|
|Journal||British Journal of Cancer|
|Publication status||Published - 31 Mar 2020|
Bibliographical noteFunding Information:
Funding information Clinical studies and WGS analyses were financially supported by Hartwig Foundation and Barcode for Life. Implementation of the data portal was supported by a grant from KWF Kankerbestrijding (HMF2017-8225, GENONCO).
Competing interests M.P.J.K.L. has advisory board memberships for Pfizer, Bayer, Roche, JnJ and received research grants from Astellas, JnJ, Sanofi and MSD. H.J.D. is an advisory board member for AstraZeneca. The other authors declare no competing interests.
© 2020, The Author(s), under exclusive licence to Cancer Research UK.