Applicability of Routine Targeted Next-generation Sequencing to Estimate Tumor Mutational Burden (TMB) in Patients Treated With Immune Checkpoint Inhibitor Therapy

Abstract

It remains unclear whether targeted next-generation sequencing (tNGS) conveys a reliable estimate of tumor mutational burden (TMB). We sequenced 79 archival samples of immune checkpoint inhibitors (ICPIs) recipients (57% lung cancer, 43% melanoma) using Ion Ampliseq Cancer Hotspot Panel. Employing multiple cutoff values, we verified that TMB by tNGS did not correlate with response or survival following ICPI. We found enrichment of ATM mutations in ICPI-refractory tumors (P=0.01) to correlate with worse survival (4.2 vs. 10 mo, P=0.03). Limited-coverage tNGS delivers an imprecise estimate of patients’ TMB but may aid identification of candidate somatic variants of predictive/prognostic significance.

Qualification of tumour mutational burden by targeted next‐generation sequencing as a biomarker in hepatocellular carcinoma

“…tNGS platforms with lower coverage and depth of sequencing have been successfully implemented as a way of testing for patients’ TMB status in tumours other than HCC 28 . Moreover, tNGS is generally suitable for analysis of FFPE samples 29 …”