Tumour mutational burden testing
Counting how many mutations a tumour carries per stretch of DNA; heavily mutated tumours are more likely to respond to immunotherapy.
Overview
Tumour mutational burden is reported by comprehensive genomic profiling panels as mutations per megabase. In June 2020 the FDA granted pembrolizumab a tissue-agnostic accelerated approval for unresectable or metastatic solid tumours with TMB of at least 10 mutations per megabase, as measured by FoundationOne CDx, based on the KEYNOTE-158 study. The threshold is contested: panel size, the inclusion of synonymous variants and germline filtering all shift the number, and the Friends of Cancer Research TMB Harmonization Project showed that different panels can disagree around the cut-off. Blood TMB from liquid biopsy panels is an emerging alternative when tissue is inadequate. TMB is most useful in cancers where PD-L1 and MSI do not explain response, such as some sarcomas and rare tumours.
How it works
Somatic non-synonymous mutations across the panel's coding territory are counted and normalised to the sequenced megabases, after filtering germline and known driver variants.
- Adds a route to immunotherapy for rare cancers
- Reported free with every large panel
- Panel-dependent values and a debated cut-off
- Weak predictive value in some cancers with high TMB such as those driven by tobacco
The FDA-approved tissue (324 genes) and blood genomic tests that serve as companion diagnostics for dozens of drugs.
The most widely used cancer immunotherapy, approved in more than 40 settings, including before and after surgery for triple-negative breast cancer.
Latest papers
topQuery for this technology: (TITLE:"Tumour mutational burden testing" OR ABSTRACT:"Tumour mutational burden testing") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Tumour mutational burden testing, not a curated reading list.
Pages like this
not linked directly; found by shared links- PersonMichael F. Berger
Shares FoundationOne CDx / Liquid CDx, Companion diagnostics, Comprehensive genomic profiling.
- TechnologyMSI and mismatch-repair testing
Shares FoundationOne CDx / Liquid CDx, Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Companion diagnostics.
- PersonAurélien Marabelle
Shares Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Pembrolizumab.
- IdeaPathologists order genomic profiling automatically at diagnosis of advanced cancer
Shares FoundationOne CDx / Liquid CDx, Companion diagnostics, Comprehensive genomic profiling.
- IdeaRegulators recognise each other's companion diagnostic approvals
Shares FoundationOne CDx / Liquid CDx, Companion diagnostics.
- CompanyLabcorp
Shares Companion diagnostics, Comprehensive genomic profiling.
- IdeaA standard evolvability score for every tumour
Shares Tumour mutational burden (TMB), Comprehensive genomic profiling.
- TermImmuno-oncology (IO) and checkpoint blockade
Shares Tumour mutational burden (TMB), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Pembrolizumab.