Science and Research

Implementing tumor mutational burden (TMB) analysis in routine diagnostics-a primer for molecular pathologists and clinicians

Tumor mutational burden (TMB) is a new biomarker for prediction of response to PD-(L)1 treatment. Comprehensive sequencing approaches (i.e., whole exome and whole genome sequencing) are ideally suited to measure TMB directly. However, as their applicability in routine diagnostics is currently limited by high costs, long turnaround times and poor availability of fresh tissue, targeted next-generation sequencing (NGS) of formalin-fixed and paraffin-embedded (FFPE) samples appears to be a more feasible and straight-forward approach for TMB approximation, which can be seamlessly integrated in already existing diagnostic workflows and pipelines. In this work, we provide an overview of the clinical implications of TMB testing and highlight key parameters including pre-analysis, analysis and post-analytical steps that influence and shape TMB approximation by panel sequencing. Collectively, the data will not only serve as a field guide and state of the art knowledge source for molecular pathologists who consider implementation of TMB measurement in their lab, but also enable clinicians in understanding the specific parameters influencing TMB test results and reporting.

  • Allgauer, M.
  • Budczies, J.
  • Christopoulos, P.
  • Endris, V.
  • Lier, A.
  • Rempel, E.
  • Volckmar, A. L.
  • Kirchner, M.
  • von Winterfeld, M.
  • Leichsenring, J.
  • Neumann, O.
  • Frohling, S.
  • Penzel, R.
  • Thomas, M.
  • Schirmacher, P.
  • Stenzinger, A.

Keywords

  • Tumor mutational burden (TMB)
  • mutational load
  • next-generation sequencing (NGS)
  • panel
  • sequencing
  • and ThermoFisher. J Leichsenring: consultancy contract with AstraZeneca. S
  • Frohling: speaker's honoraria from Amgen, Lilly, PharmaMar and Roche
  • research
  • funding from AstraZeneca, Pfizer and PharmaMar. M Thomas: advisory board
  • honoraria from Novartis, Lilly, BMS, MSD, Roche, Celgene, Takeda, AbbVie,
  • Boehringer, speaker's honoraria from Lilly, MSD, Takeda, research funding from
  • AstraZeneca, BMS, Celgene, Novartis, Roche and travel grants from BMS, MSD,
  • Novartis, Boehringer. P Schirmacher: advisory board honoraria from Pfizer, Roche,
  • Novartis, AstraZeneca as well as speaker's honoraria and research funding from
  • Roche, AstraZeneca and Novartis. A Stenzinger: advisory board honoraria from BMS,
  • AstraZeneca, Novartis, ThermoFisher, speaker's honoraria from BMS, Illumina,
  • AstraZeneca, MSD, Novartis, Roche, ThermoFisher, and research funding from
  • Chugai. The other authors have no conflicts of interest to declare.
Publication details
DOI: 10.21037/tlcr.2018.08.14
Journal: Translational lung cancer research
Pages: 703-715 
Number: 6
Work Type: Review
Location: TLRC
Disease Area: LC
Partner / Member: DKFZ, Thorax
Access-Number: 30505715
See publication on PubMed

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