TMB standardization by alignment to reference standards: Phase II of the Friends of Cancer Research TMB Harmonization Project.

• DOI: 10.1200/jco.2019.37.15_suppl.2624
• Publication Date: 2019-05-27T15:58:33Z
• Authors: Diana M. Merino; Lisa McShane; Matt Butler; Vincent Anthony F...; Matthew David Hel...; Ruchi Chaudhary; Shu-Jen Chen; Wangjuh Sting Chen; Jeffrey M. Conroy; David Fabrizio; Laura E MacConaill; Aparna Pallavajjala; Arnaud Papin; Mark Sausen; Victor J Weigman; Mingchao Xie; Ahmet Zehir; Chen Zhao; Paul M. Williams
• Keywords: Harmonization

2624 Background: Tumor mutational burden (TMB) is a predictive biomarker of response to immune checkpoint inhibitors across multiple cancers. In Phase 1 the Friends Cancer Research Harmonization Project, we demonstrated robust correlation between TMB estimated using targeted next-generation sequencing (NGS) gene panels and whole exome (WES) applied MC3-TCGA data. These findings variability in estimates different panels. 2 evaluates sustainable reference standard materials for alignment assess this variability. The goal effort establish best practices estimating order improve consistency panels, sake optimizing clinical application facilitating integration datasets generated from assays. Methods: Fifteen laboratories with at stages development participated. We identified set standards consisting 10 well-characterized human-derived lung breast tumor-normal matched cell lines. WES was performed uniform bioinformatics pipeline agreed upon by all team members (WES-TMB). Each laboratory used their own pipelines (tumor-only tumor-normal) estimate according genes represented respective (panel-TMB). association WES-TMB each panel-TMB investigated regression analyses. Bias (relative WES-TMB) were rigorously assessed. All analyses blinded. Results: spanned clinically meaningful range (4.3 31.4 mut/Mb). Preliminary data 12 shows good empirical analysis. Across R values 0.77-0.96 slopes ranging 0.60-1.26. Calibration that seek minimize established are ongoing, as well investigating cancer type dependence on relationship vs. WES-TMB, which will be available time presentation. Conclusions: demonstrate feasibility control lines standardize align estimation NGS Future studies aim validate material reliable tool formalin-fixed paraffin-embedded human tumor samples.