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  • Title: Tumor mutational burden on cytological samples: A pilot study.
    Author: Pepe F, Pisapia P, Gristina V, Rocco D, Micheli M, Micheli P, Iaccarino A, Tufano R, Gragnano G, Russo G, De Luca C, Sgariglia R, Nacchio M, Girolami I, Eccher A, Russo A, Troncone G, Malapelle U.
    Journal: Cancer Cytopathol; 2021 Jun; 129(6):460-467. PubMed ID: 33378102.
    Abstract:
    BACKGROUND: Immune-checkpoint inhibitors (ICIs) represent an important treatment option for patients who have advanced stage non-small cell lung cancer (NSCLC). Currently, evaluation of the expression level of programmed death-ligand 1 (PD-L1) has proven highly successful as a positive predictive biomarker for ICIs. In addition to PD-L1, other promising predictive biomarkers are emerging, including high tumor mutational burden (TMB-H). However, measuring TMB-H remains challenging for several reasons, among which is the difficulty in obtaining adequate tissue material from NSCLC patients. There are no data in the current literature regarding the possibility of adopting cell blocks (CBs) for TMB evaluation; therefore, our goal was to evaluate the feasibility of analyzing TMB on CBs. METHODS: For evaluation of differences in run metric parameters, 8 pairs of histological and CB samples from patients with NSCLC were analyzed using the Oncomine Tumor Mutational Load Assay on Ion Torrent S5 GS next-generation sequencing (NGS) platform. RESULTS: Most CBs (6/8, 75.0%) were successfully analyzed by adopting the broad NGS panel approach. CBs provided results similar to those obtained on histological matched specimens in terms of median total reads (7207048.80 vs 7558817.80), median mapped reads (7075753.83 vs 7513822.00), median read lengths (115.50 vs. 113.00), median percentage of reads on-target (97.49% vs. 98.45%), median average reads per amplicon (454.67 vs 476.14), and median uniformity of amplicon coverage (83.52% vs 84.13%). CONCLUSION: In this pilot study, we demonstrated the technical feasibility of assessing TMB on CBs.
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