title: Data Interoperability of Whole Exome Sequencing (WES) Based Mutational Burden Estimates from Different Laboratories.
abstract: Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. Several independent studies suggest that higher non-synonymous mutational burden assessed by whole exome sequencing (WES) in tumors is associated with improved objective response, durable clinical benefit, and progression-free survival in immune checkpoint inhibitors treatment. Next-generation sequencing (NGS) is a promising technology being used in the clinic to direct patient treatment. Cancer genome WES poses a unique challenge due to tumor heterogeneity and sequencing artifacts introduced by formalin-fixed, paraffin-embedded (FFPE) tissue. In order to evaluate the data interoperability of WES data from different sources to survey tumor mutational landscape, we compared WES data of several tumor/normal matched samples from five commercial vendors. A large data discrepancy was observed from vendors' self-reported data. Independent data analysis from vendors' raw NGS data shows that whole exome sequencing data from qualified vendors can be combined and analyzed uniformly to derive comparable quantitative estimates of tumor mutational burden.
authors.affiliation: Translational Molecular Biomarkers, Merck Research Laboratories, Merck &amp; Co., Inc., 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. ping.qiu@merck.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Qiu
authors.affiliation: Translational Molecular Biomarkers, Merck Research Laboratories, Merck &amp; Co., Inc., 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. ling.pang@merck.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Pang
authors.affiliation: Translational Molecular Biomarkers, Merck Research Laboratories, Merck &amp; Co., Inc., 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. gladys.arreaza@merck.com.
authors.forename: Gladys
authors.initials: G
authors.lastname: Arreaza
authors.affiliation: Translational Molecular Biomarkers, Merck Research Laboratories, Merck &amp; Co., Inc., 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. maureen.maguire@merck.com.
authors.forename: Maureen
authors.initials: M
authors.lastname: Maguire
authors.affiliation: Translational Molecular Biomarkers, Merck Research Laboratories, Merck &amp; Co., Inc., 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. ken.chang@merck.com.
authors.forename: Ken C N
authors.initials: KC
authors.lastname: Chang
authors.affiliation: Companion Diagnostics, Translational Biomarkers, Merck Research Laboratories, Merck &amp; Co., Inc., 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. matthew_marton@merck.com.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Marton
authors.affiliation: Translational Molecular Biomarkers, Merck Research Laboratories, Merck &amp; Co., Inc., 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. diane.levitan@merck.com.
authors.forename: Diane
authors.initials: D
authors.lastname: Levitan
mesh_terms: D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007753:Laboratories; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016612:Paraffin Embedding; D017422:Sequence Analysis, DNA
keywords: PD-1; immune checkpoint inhibitor; mutational burden; next generation sequencing (NGS); whole exome sequencing (WES)