Improving the detection of patients with inherited predispositions to hematologic malignancies using next-generation sequencing-based leukemia prognostication panels

Courtney D. DiNardo, Mark J. Routbort, Sarah A. Bannon, Christopher B. Benton, Koichi Takahashi, Steve M. Kornblau, Rajyalakshmi Luthra, Rashmi Kanagal-Shamanna, L. Jeffrey Medeiros, Guillermo Garcia-Manero, Hagop M. Kantarjian, P. Andrew Futreal, Funda Meric-Bernstam, Keyur P. Patel

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations

Abstract

Recognizing and referring patients with possible inherited cancer predisposition syndromes for appropriate genetic evaluation and testing provides insights into optimal patient treatment approaches and also can provide education and testing opportunities for family members. Next-generation sequencing (NGS)-based, targeted genotyping for somatic mutations is increasingly used in the diagnosis, prognostication, and treatment selection for patients with hematologic malignancies. However, certain mutations that may be somatically acquired can also be present as germline mutations in some individuals and families. Whether the results of NGS-based leukemia panels can be used to inform decisions and subsequent evaluation of patients with possible inherited cancer predispositions has not been described previously. Because a normal control often is not available when using NGS panels in patients with hematologic malignancies, NGS panel results offer both an opportunity and a challenge to determine the origin and pathogenicity of identified mutations. In the absence of a matched germline control, variant allele frequency (VAF) estimation and data from publically available data sets provide important clues to the possible germline origin of a variant. Careful annotation and review of NGS panels in patients with hematologic malignancies can provide a useful screening tool to systematically improve upon the detection of potentially pathogenic germline variants. Cancer 2018;124:2704-2713.

Original languageEnglish
Pages (from-to)2704-2713
Number of pages10
JournalCancer
Volume124
Issue number13
DOIs
StatePublished - 1 Jul 2018
Externally publishedYes

Keywords

  • gene panel
  • germline
  • inherited
  • mutation
  • next-generation sequencing (NGS)

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