PMID- 34358677 OWN - NLM STAT- MEDLINE DCOM- 20220208 LR - 20220208 IS - 1943-7811 (Electronic) IS - 1525-1578 (Linking) VI - 23 IP - 10 DP - 2021 Oct TI - Diagnostic Utility of Gene Fusion Panel to Detect Gene Fusions in Fresh and Formalin-Fixed, Paraffin-Embedded Cancer Specimens. PG - 1343-1358 LID - S1525-1578(21)00239-7 [pii] LID - 10.1016/j.jmoldx.2021.07.015 [doi] AB - Somatic gene fusions are common in leukemias/lymphomas and solid tumors. The detection of gene fusions is crucial for diagnosis. NanoString fusion technology is a multiplexed hybridization method that interrogates hundreds of gene fusions in a single reaction. This study's objective was to determine the performance characteristics and diagnostic utility of NanoString fusion assays in a clinical diagnostics laboratory. Validation using 100 positive specimens and 15 negative specimens by a combined reference standard of fluorescence in situ hybridization (FISH)/RT-PCR/next-generation sequencing (NGS) assays achieved 100% sensitivity in leukemias/lymphomas and 95.0% sensitivity and 100% specificity in solid tumors. Subsequently, 214 consecutive clinical cases, including 73 leukemia/lymphoma specimens and 141 formalin-fixed, paraffin-embedded solid tumor specimens, were analyzed by gene fusion panels across 638 unique gene fusion transcripts. A variety of comparator tests, including FISH panels, conventional karyotyping, a DNA-based targeted NGS assay, and custom RT-PCR testing, were performed in parallel. The gene fusion assay detected 31 gene fusions, including 16 in leukemia/lymphoma specimens and 15 in solid tumor specimens. The overall sensitivity, specificity, and accuracy of gene fusions detected by the gene fusion panel in all 329 specimens (validation and consecutive clinical specimens) tested in this study were 94.8%, 100%, and 97.9%, respectively, compared with FISH/RT-PCR/NGS assays. The gene fusion panel is a reliable approach that maximizes molecular detection of fusions among both fresh and formalin-fixed, paraffin-embedded cancer specimens. CI - Copyright (c) 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. FAU - Haley, Lisa AU - Haley L AD - Johns Hopkins Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Parimi, Vamsi AU - Parimi V AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Jiang, Liqun AU - Jiang L AD - Johns Hopkins Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Pallavajjala, Aparna AU - Pallavajjala A AD - Johns Hopkins Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Hardy, Melanie AU - Hardy M AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Cytogenetics Laboratory, Johns Hopkins University Hospital, Baltimore, Maryland. FAU - Yonescu, Raluca AU - Yonescu R AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Cytogenetics Laboratory, Johns Hopkins University Hospital, Baltimore, Maryland. FAU - Morsberger, Laura AU - Morsberger L AD - Johns Hopkins Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Cytogenetics Laboratory, Johns Hopkins University Hospital, Baltimore, Maryland. FAU - Stinnett, Victoria AU - Stinnett V AD - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Cytogenetics Laboratory, Johns Hopkins University Hospital, Baltimore, Maryland. FAU - Long, Patty AU - Long P AD - Johns Hopkins Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Cytogenetics Laboratory, Johns Hopkins University Hospital, Baltimore, Maryland. FAU - Zou, Ying S AU - Zou YS AD - Johns Hopkins Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Cytogenetics Laboratory, Johns Hopkins University Hospital, Baltimore, Maryland. Electronic address: yzou19@jh.edu. FAU - Gocke, Christopher D AU - Gocke CD AD - Johns Hopkins Genomics, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Study DEP - 20210804 PL - United States TA - J Mol Diagn JT - The Journal of molecular diagnostics : JMD JID - 100893612 RN - 0 (Biomarkers, Tumor) RN - 0 (Fixatives) RN - 1HG84L3525 (Formaldehyde) SB - IM MH - Adenocarcinoma of Lung/diagnosis/*genetics/pathology MH - Biomarkers, Tumor/genetics MH - Biopsy/methods MH - *Fixatives MH - *Formaldehyde MH - *Gene Fusion MH - High-Throughput Nucleotide Sequencing/methods MH - Humans MH - In Situ Hybridization, Fluorescence/methods MH - Karyotyping/methods MH - Leukemia/diagnosis/*genetics/pathology MH - Limit of Detection MH - Lung Neoplasms/diagnosis/*genetics/pathology MH - Lymphoma/diagnosis/*genetics/pathology MH - Molecular Diagnostic Techniques/methods MH - *Paraffin Embedding MH - Prospective Studies MH - Reproducibility of Results MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Sequence Analysis, DNA/methods MH - Sequence Analysis, RNA/methods EDAT- 2021/08/07 06:00 MHDA- 2022/02/09 06:00 CRDT- 2021/08/06 20:13 PHST- 2021/02/28 00:00 [received] PHST- 2021/06/04 00:00 [revised] PHST- 2021/07/08 00:00 [accepted] PHST- 2021/08/07 06:00 [pubmed] PHST- 2022/02/09 06:00 [medline] PHST- 2021/08/06 20:13 [entrez] AID - S1525-1578(21)00239-7 [pii] AID - 10.1016/j.jmoldx.2021.07.015 [doi] PST - ppublish SO - J Mol Diagn. 2021 Oct;23(10):1343-1358. doi: 10.1016/j.jmoldx.2021.07.015. Epub 2021 Aug 4.