Tumor Mutation Burden Computation in Two Pan-Cancer Precision Medicine Next-Generation Sequencing Panels

J Comput Biol. 2020 Oct;27(10):1553-1560. doi: 10.1089/cmb.2019.0055. Epub 2020 Apr 20.

Abstract

FD-180 and FD-600 are two next-generation sequencing panels developed by First Dimension Biosciences Co. for detecting mutations in cancer tissues and providing therapeutics guidance in precision medicine applications. FD-180 includes the coding exons of about 180 genes, including all the known drug target genes and some important driver genes; whereas FD-600 includes the coding exons of 578 cancer driver genes in the COSMIC database as of year 2016 when the panels are developed. Additional noncoding regions in the selected genes are included if they are reported as clinically meaningful in ClinVar. Tumor mutation burden (TMB) is a statistical index calculated from genomic sequencing for immunotherapeutic treatments, especially for PD1/PD-L1 antibodies. We used our computational algorithm on 81 patients and provided their classifications. TMB can be estimated quite accurately for the FD-180 and FD-600 panels, both for The Cancer Genome Atlas data and in clinical practice.

Keywords: cancer driver genes; immunotherapeutics; next-generation sequencing; precision medicine; tumor mutation burden; whole-exome sequencing.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Biomarkers, Tumor / genetics*
  • Child
  • Child, Preschool
  • Computational Biology
  • Exome / genetics
  • Female
  • High-Throughput Nucleotide Sequencing / methods*
  • High-Throughput Nucleotide Sequencing / statistics & numerical data
  • Humans
  • INDEL Mutation
  • Immunotherapy
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasms / genetics*
  • Neoplasms / therapy
  • Polymorphism, Single Nucleotide
  • Precision Medicine
  • Young Adult

Substances

  • Biomarkers, Tumor