Designing Myeloid Gene Panels

Abstract

Context.— Next-generation sequencing studies are increasingly used in the evaluation of suspected chronic myeloid neoplasms (CMNs), but there is wide variability among laboratories in the genes analyzed for this purpose. Recently, the Association for Molecular Pathology CMN working group recommended a core 34-gene set as a minimum target list for evaluation of CMNs. This list was recommended based on literature review, and its diagnostic yield in clinical practice is unknown. Objective.— To determine the diagnostic yield of the core 34 genes and assess the potential impact of including selected additional genes. Design.— We retrospectively reviewed 185 patients with known or suspected CMNs tested using a 62-gene next-generation sequencing panel that included all 34 core genes. Results.— The Association for Molecular Pathology's core 34 genes had a diagnostic yield of 158 of 185 (85.4%) to detect at least 1 variant with strong/potential clinical significance and 107 of 185 (57.8%) to detect at least 2 such variants. The 62-gene panel had a diagnostic yield of 160 of 185 (86.5%) and 112 of 185 (60.5%), respectively. Variants of unknown significance were identified in 49 of 185 (26.5%) using the core 34 genes versus 76 of 185 (41.1%) using the 62-gene panel. Conclusions.— This study demonstrates that the Association for Molecular Pathology–recommended core 34-gene set has a high diagnostic yield in CMNs. Inclusion of selected additional genes slightly increases the rate of abnormal results, while also increasing the detection of variants of unknown significance. We recommend inclusion of CUX1, DDX41, ETNK1, RIT1, and SUZ12 in addition to the Association for Molecular Pathology's 34-gene core set for routine evaluation of CMNs.