Tumor mutational burden (TMB) predicts the response of some tumor types to immune checkpoint inhibitor therapy. However, TMB is an imperfect biomarker as some patients respond conversely to expectation. One partial explanation for the observed discrepancies is that some or many of the mutations contributing to TMB are not expressed and do not produce neoantigens.
This whitepaper from SeraCare compares TMB as measured by whole-exome sequencing with expression of TMB mutations in whole-transcriptome sequences. The study authors compared two library prep techniques, differing mainly in their ribodepletion methods. They found that the resulting whole-transcriptome libraries showed reproducibility within and between methods, and that approximately half of the TMB mutations called by exome sequencing have no or very little expression in the tumor cell lines assessed.
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