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Published on: April 11, 2016
Tumor mutation burden testing: a survey of the International Quality Network for Pathology (IQN Path)
Francesca Fenizia1, Nicola Wolstenholme2, Jennifer A Fairley3
1Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori - IRCCS - "Fondazione G. Pascale", Via Mariano Semola, 80131, Napoli, Italy.
Abstract:
While tumour mutation burden (TMB) is emerging as a possible biomarker for immune-checkpoint inhibitors (ICI), methods for testing have not been standardised as yet. In April 2019, the International Quality Network for Pathology (IQN Path) launched a survey to assess the current practice of TMB testing. Of the 127 laboratories that replied, 69 (54.3%) had already introduced TMB analysis for research purposes and/or clinical applications. Fifty laboratories (72.5%) used targeted sequencing, although a number of different panels were employed. Most laboratories tested formalin-fixed paraffin-embedded material (94.2%), while 18/69 (26%) tested also cell-free DNA. Fifty-five laboratories used both single nucleotide variants and indels for TMB calculation; 20 centers included only non-synonymous variants. In conclusion, the data from this survey indicate that multiple global laboratories were capable of rapidly introducing routine clinical TMB testing. However, the variability of testing methods raises concerns about the reproducibility of results among centers.
Insights
Tumor mutation burden (TMB) testing for immune-checkpoint inhibitors (ICI) is becoming common, but methods vary significantly. This variability raises concerns about the reproducibility of TMB results across different laboratories worldwide.
Area of Science:
- Oncology
- Genomics
- Pathology
Background:
- Tumor mutation burden (TMB) is a potential biomarker for predicting response to immune-checkpoint inhibitors (ICI).
- Standardization of TMB testing methods is currently lacking, posing challenges for clinical implementation.
Purpose of the Study:
- To assess the current practices and variability in TMB testing among global laboratories.
- To understand the adoption rate of TMB analysis for research and clinical applications.
Main Methods:
- A survey was conducted by the International Quality Network for Pathology (IQN Path) in April 2019.
- The survey targeted 127 laboratories to gather data on TMB testing methodologies, including sequencing approaches, sample types, and variant calling criteria.
Main Results:
- 54.3% of responding laboratories had implemented TMB analysis.
- Targeted sequencing was the predominant method (72.5%), with diverse panels used.
- Formalin-fixed paraffin-embedded (FFPE) tissue was the most common sample type (94.2%), with some laboratories also analyzing cell-free DNA (26%).
- Variations were observed in the types of variants included for TMB calculation (SNVs, indels, or non-synonymous variants).
Conclusions:
- Global laboratories demonstrate the capability to rapidly implement routine clinical TMB testing.
- Significant variability in TMB testing methodologies across laboratories raises concerns regarding result reproducibility and clinical utility.
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