Impact of panel design and cut-off on tumour mutational burden assessment in metastatic solid tumour samples

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 d...

Full description

Saved in:
Bibliographic Details
Published inBritish journal of cancer Vol. 122; no. 7; pp. 953 - 956
Main Authors Mankor, Joanne M., Paats, Marthe S., Groenendijk, Floris H., Roepman, Paul, Dinjens, Winand N. M., Dubbink, Hendrikus J., Sleijfer, Stefan, Cuppen, Edwin, Lolkema, Martijn P. J. K.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.03.2020
Nature Publishing Group
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-020-0762-5