Design and Application of Multiplex PCR Seq for the Detection of Somatic Mutations Associated with Myeloid Malignancies

Methods Mol Biol. 2017:1633:87-99. doi: 10.1007/978-1-4939-7142-8_6.

Abstract

Targeted sequencing, in which only a selected set of genomic loci are sequenced, enables a much higher coverage of each target than what is obtained using whole genome or exome sequencing. Multiplex PCR offers a simple and affordable technique for specific capture of target regions and can be easily adapted to generate next-generation sequencing (NGS)-ready amplicons. Here we describe a multiplex PCR (MxPCR) approach for capturing 13 leukemia-associated mutation hotspots followed by MiSeq sequencing that enables robust detection of mutations with a variant allele fraction (VAF) as low as 0.8% (0.008) in blood DNA.

Keywords: Clonal hemopoiesis; Leukemia; Multiplex PCR; Targeted sequencing.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Multiplex Polymerase Chain Reaction / methods*
  • Mutation*
  • Myeloproliferative Disorders / diagnosis*
  • Myeloproliferative Disorders / genetics
  • Research Design
  • Sequence Analysis, DNA / methods*

Substances

  • Biomarkers, Tumor