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Published on: January 12, 2020
Tumour Mutational Burden and Its Relationship with Clinical Outcomes in Locally Advanced and Recurrent/Metastatic
Karan Patel1, Joseph Edward Haigh1, Samuel Rack1
1The Christie NHS Foundation Trust, Wilmslow Road, Manchester M20 4BX, UK.
Background/Objectives:
Adenoid 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.
Methods:
124 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.
Results:
Median 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, p = 0.02) in the NHS group.
Conclusions:
LA-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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