Assessment of technical heterogeneity among diagnostic tests to detect germline risk variants for hematopoietic malignancies

Gregory W. Roloff, Lucy A. Godley, Michael W. Drazer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Purpose: To determine the degree of testing consistency among commercially available diagnostic assays for hereditary hematopoietic malignancies (HHMs). Methods: Next-generation sequencing assays designed for the diagnosis of HHMs were studied to determine which genes were sequenced, their ability to detect variant types relevant for HHMs, and clinical-grade characteristics such as price, turnaround time, and tissue types accepted. Results: Commercial assays varied in price (USD 250–4702), number of genes sequenced (12–73), and average turnaround time (14–42 days). A number of nongermline tissue types were accepted despite the tests being designed for germline diagnostic purposes. Multiple genes with well-characterized roles in HHM pathogenesis were omitted from more than one-third of panels intended for the evaluation of HHMs. Only 4 of 82 genes were consistently covered across all HHM diagnostic panels. The assays were highly variable in their sensitivity for structural alterations relevant to HHMs, such as copy-number variants. Conclusion: A high degree of diagnostic heterogeneity exists among commercially available HHM diagnostic assays. Many of these assays are incapable of detecting the full spectrum of HHM-associated variants, leaving patients vulnerable to the consequences of underdiagnosis, missed opportunities for screening, and the potential for donor-derived malignancies.

Original languageEnglish (US)
Pages (from-to)211-214
Number of pages4
JournalGenetics in Medicine
Issue number1
StatePublished - Jan 2021


  • cancer risk
  • germline
  • hematopoietic malignancies
  • inherited leukemia
  • panel testing

ASJC Scopus subject areas

  • Genetics(clinical)


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