Integration of next-generation sequencing in clinical diagnostic molecular pathology laboratories for analysis of solid tumours; an expert opinion on behalf of IQN Path ASBL

In the present study, we analysed 44 formalin fixed paraffin embedded (FFPE) from different solid tumours by adopting two different next generation sequencing platforms: GeneReader (QIAGEN, Hilden, Germany) and Ion Torrent (Thermo Fisher Scientific, Waltham, Massachusetts, USA). We highlighted a 100% concordance between the platforms. In addition, focusing on variant detection, we evaluated a very good agreement between the two tests (Cohen’s kappa=0.84) and, when taking into account variant allele fraction value for each variant, a very high concordance was obtained (Pearson’s r=0.94). Our results underlined the high performance rate of GeneReader on FFPE samples and its suitability in routine molecular predictive practice.

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Designing Myeloid Gene Panels

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2021-0124-oa ◽

2021 ◽

Author(s):

Fang Zhao ◽

David S. Bosler ◽

James R. Cook

Keyword(s):

Next Generation Sequencing ◽

Molecular Pathology ◽

Diagnostic Yield ◽

Gene Panel ◽

Next Generation ◽

Gene Set ◽

Variants Of Unknown Significance ◽

The Core ◽

Unknown Significance ◽

Generation Sequencing

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.

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