ArticleCancers2026
Tumour Mutational Burden and Its Relationship with Clinical Outcomes in Locally Advanced and Recurrent/Metastatic Adenoid Cystic Carcinoma with and Without NOTCH Pathway Activation.
Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND/
objectivesAdenoid cystic carcinoma (ACC) is a heterogenous disease and defining aggressive subtypes to inform surveillance and treatment strategies remains clinically pertinent. NOTCH pathway-activated ACC is associated with worse outcomes. We describe the distribution of tumour mutational burden (TMB) and characterise its relationship with NOTCH gain-of-function (GoF) mutation and survival in locally advanced or recurrent/metastatic (LA-R/M) ACC.
methods124 tumours from the UK NHS (NHS group) and 139 tumours from cBioPortal; MSK metTropism (MSK group) were evaluated as independent cohorts. TMB (mut/Mb) was calculated either by F1CDx or its precursor FoundationOne NGS in the NHS group, or MSK-IMPACT NGS in the MSK group. NOTCH1/2 mutations were classed as GoF if predicted to disrupt the NRR/PEST domains. Overall survival (OS) was measured from diagnosis of unresectable LA-R/M ACC.
resultsMedian TMB was 1.26 mut/Mb (IQR 0-2.52) in the NHS group and 1.96 (IQR 0.87-3.46) in the MSK group. NOTCH1/2 GoF mutation was seen in 16/124 (13%) in the NHS group and 22/139 (16%) in the MSK group. Median TMB for tumours with NOTCH1/2 GoF mutation was 2.52 mut/Mb (IQR 1.82-3.84) in the NHS group and 4.38 mut/Mb (IQR 3.33-4.89) in the MSK group. For tumours with NOTCH1/2 GoF mutation, median OS reduced with TMB > median of 2.52 mut/Mb (0.7 yrs vs. 2.6 yrs,
conclusionsLA-R/M ACC has a low TMB profile overall. Median TMB was higher in NOTCH-activated ACC in both the NHS and MSK groups and TMB may have value in further stratifying patients with LA-R/M ACC.
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