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Updated: Dec 11, 2025
Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
Assessment of technical heterogeneity among diagnostic tests to detect germline risk variants for hematopoietic
Gregory W Roloff1, Lucy A Godley2,3, Michael W Drazer4,5
1Department of Medicine, Loyola University Medical Center, Maywood, IL, USA.
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.
