Development and Clinical Validation of a Multiplex Gene Fusion Assay

被引：7
作者：
Garcia, Rolando [1 ,2 ]
Patel, Nirav [2 ]
Uddin, Naseem [1 ,2 ]
Park, Jason Y. [1 ,2 ,3 ]
机构：
[1] UT Southwestern Med Ctr, Dept Pathol, Dallas, TX 75390 USA
[2] Childrens Med Ctr, Dept Pathol, Dallas, TX 75235 USA
[3] UT Southwestern Med Ctr, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA
来源：
LABORATORY MEDICINE | 2020年 / 51卷 / 05期
关键词：
anchored multiplex PCR sequencing; gene fusion events; pediatric tumors; RNAseq; gene fusion; anchored multiplex; genomic; pediatric oncology;
D O I：
10.1093/labmed/lmz102
中图分类号：
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号：
1001 ;
摘要：
Objective: The detection of gene fusion events is important for the diagnosis and management of malignancies. In this study, we describe the validation of a next-generation sequencing assay for multiplex detection of gene fusions. Methods: Based on previously described gene fusion events that occur in pediatric oncology, a custom anchored multiplex next-generation sequencing assay was designed to target 93 genes. Results: A total of 24 previously characterized specimens were examined. Twenty specimens had 1 or more previously described fusion events, and 4 specimens were negative for fusion events. The accuracy across specimens was 100% (20 of 20 specimens). The analytical sensitivity and specificity were both 100%. Interday reproducibility for fusion events was 94%; in comparison, intraday reproducibility was 90%. Conclusion: This multiple-gene fusion assay demonstrated appropriate sensitivity, specificity, and accuracy for clinical use. We anticipate that this assay will improve the diagnosis and management of patients with pediatric solid tumors.
引用
收藏
页码：512 / 518
页数：7
相关论文
共 11 条
  • [1] NTRK fusion-positive cancers and TRK inhibitor therapy
    Cocco, Emiliano
    Scaltriti, Maurizio
    Drilon, Alexander
    [J]. NATURE REVIEWS CLINICAL ONCOLOGY, 2018, 15 (12) : 731 - 747
  • [2] THE EWING FAMILY OF TUMORS - A SUBGROUP OF SMALL-ROUND-CELL TUMORS DEFINED BY SPECIFIC CHIMERIC TRANSCRIPTS
    DELATTRE, O
    ZUCMAN, J
    MELOT, T
    GARAU, XS
    ZUCKER, JM
    LENOIR, GM
    AMBROS, PF
    SHEER, D
    TURCCAREL, C
    TRICHE, TJ
    AURIAS, A
    THOMAS, G
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (05) : 294 - 299
  • [3] Fusion Status in Patients With Lymph Node-Positive (N1) Alveolar Rhabdomyosarcoma Is a Powerful Predictor of Prognosis: Experience of the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG)
    Gallego, Soledad
    Zanetti, Ilaria
    Orbach, Daniel
    Ranchere, Dominique
    Shipley, Janet
    Zin, Angelica
    Bergeron, Christophe
    de Salvo, Gian Luca
    Chisholm, Julia
    Ferrari, Andrea
    Jenney, Meriel
    Mandeville, Henry C.
    Rogers, Timothy
    Merks, Johannes H. M.
    Mudry, Peter
    Glosli, Heidi
    Milano, Giuseppe Maria
    Ferman, Sima
    Bisogno, Gianni
    [J]. CANCER, 2018, 124 (15) : 3201 - 3209
  • [4] Molecular characterization of cancers with NTRK gene fusions
    Gatalica, Zoran
    Xiu, Joanne
    Swensen, Jeffrey
    Vranic, Semir
    [J]. MODERN PATHOLOGY, 2019, 32 (01) : 147 - 153
  • [5] Guidelines for Validation of Next-Generation Sequencing-Based Oncology Panels A Joint Consensus Recommendation of the Association for Molecular Pathology and College of American Pathologists
    Jennings, Lawrence J.
    Arcila, Maria E.
    Corless, Christopher
    Kamel-Reid, Suzanne
    Lubin, Ira M.
    Pfeifer, John
    Temple-Smolkin, Robyn L.
    Voelkerding, Karl V.
    Nikiforova, Marina N.
    [J]. JOURNAL OF MOLECULAR DIAGNOSTICS, 2017, 19 (03) : 341 - 365
  • [6] A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma
    Knezevich, SR
    McFadden, DE
    Tao, W
    Lim, JF
    Sorensen, PHB
    [J]. NATURE GENETICS, 1998, 18 (02) : 184 - 187
  • [7] Infantile Fibrosarcoma With NTRK3-ETV6 Fusion Successfully Treated With the Tropomyosin-Related Kinase Inhibitor LOXO-101
    Nagasubramanian, Ramamoorthy
    Wei, Julie
    Gordon, Paul
    Rastatter, Jeff C.
    Cox, Michael C.
    Pappo, Alberto
    [J]. PEDIATRIC BLOOD & CANCER, 2016, 63 (08) : 1468 - 1470
  • [8] Pediatric Treatment Editorial Board, PDQ CHILDH CANC GEN
  • [9] BCOR-CCNB3 fusions are frequent in undifferentiated sarcomas of male children
    Peters, Tricia L.
    Kumar, Vijetha
    Polikepahad, Sumanth
    Lin, Frank Y.
    Sarabia, Stephen F.
    Liang, Yu
    Wang, Wei-Lien
    Lazar, Alexander J.
    Doddapaneni, HarshaVardhan
    Chao, Hsu
    Muzny, Donna M.
    Wheeler, David A.
    Okcu, M. Fatih
    Plon, Sharon E.
    Hicks, M. John
    Lopez-Terrada, Dolores
    Parsons, D. Williams
    Roy, Angshumoy
    [J]. MODERN PATHOLOGY, 2015, 28 (04) : 575 - 586
  • [10] NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis
    Struski, S.
    Lagarde, S.
    Bories, P.
    Puiseux, C.
    Prade, N.
    Cuccuini, W.
    Pages, M-P
    Bidet, A.
    Gervais, C.
    Lafage-Pochitaloff, M.
    Roche-Lestienne, C.
    Barin, C.
    Penther, D.
    Nadal, N.
    Radford-Weiss, I.
    Collonge-Rame, M-A
    Gaillard, B.
    Mugneret, F.
    Lefebvre, C.
    Bart-Delabesse, E.
    Petit, A.
    Leverger, G.
    Broccardo, C.
    Luquet, I.
    Pasquet, M.
    Delabesse, E.
    [J]. LEUKEMIA, 2017, 31 (03) : 565 - 572
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