PMID- 33571894 OWN - NLM STAT- MEDLINE DCOM- 20211019 LR - 20211019 IS - 2210-7762 (Print) VI - 254-255 DP - 2021 Jun TI - A multimodal genomics approach to diagnostic evaluation of pediatric hematologic malignancies. PG - 25-33 LID - S2210-7762(21)00007-7 [pii] LID - 10.1016/j.cancergen.2021.01.007 [doi] AB - Detection of somatic genetic drivers is important for risk stratification and treatment selection in pediatric leukemias; however, newly recognized genetic markers may not be detected by routine karyotyping and fluorescence in situ hybridization (FISH). To identify the combination of assays that provides the highest detection rate for clinically significant molecular abnormalities, we tested 160 B- lymphoblastic leukemia (B-ALL) by karyotyping, FISH, chromosomal microarray analysis (CMA) and the custom next-generation sequencing (NGS) panel, OncoKids(Ⓡ). In addition, we tested 40 myeloid malignancies with karyotyping, chromosomal microarray analysis (CMA), and OncoKids(Ⓡ); 36/40 myeloid malignancies were also tested with FISH. In B-ALL, individual testing methods had the following diagnostic yields for the key genetic drivers: karyotype 34%; basic FISH panel 45%; FISH panel with IGH and CRLF2 probes 65%; CMA 48%; OncoKids(Ⓡ) 39%. CMA and OncoKids(Ⓡ) testing allowed detection of key genetic drivers in 42% of the samples that remained unknown upon testing by conventional methods. In myeloid malignancies, OncoKids(Ⓡ) had the highest yield for detection of both primary and secondary DNA mutations and RNA fusions. Our data highlights the complementarity between CMA and NGS and conventional cytogenetics/FISH in pediatric leukemia diagnostics. Due to rapid turn-around-time, FISH may be useful as an initial screening method in B-ALL. Our data also suggests NGS testing with a comprehensive panel, despite a longer turnaround time, is a good alternative to karyotyping and FISH in pediatric AML due to its superior detection rate. CI - Copyright (c) 2021. Published by Elsevier Inc. FAU - Hiemenz, Matthew C AU - Hiemenz MC AD - Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, United States; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Oberley, Matthew J AU - Oberley MJ AD - Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, United States; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Doan, Andrew AU - Doan A AD - Division of Hematology-Oncology, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Aye, Le AU - Aye L AD - Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, United States; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Ji, Jianling AU - Ji J AD - Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, United States; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Schmidt, Ryan J AU - Schmidt RJ AD - Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, United States; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Biegel, Jaclyn A AU - Biegel JA AD - Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, United States; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Bhojwani, Deepa AU - Bhojwani D AD - Division of Hematology-Oncology, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Raca, Gordana AU - Raca G AD - Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, United States; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. Electronic address: graca@chla.usc.edu. LA - eng PT - Journal Article DEP - 20210121 PL - United States TA - Cancer Genet JT - Cancer genetics JID - 101539150 RN - 0 (Oncogene Proteins, Fusion) SB - IM MH - Child MH - Cohort Studies MH - *Genomics MH - Germ-Line Mutation/genetics MH - Hematologic Neoplasms/*diagnosis/*genetics MH - Humans MH - Incidence MH - Oncogene Proteins, Fusion/genetics MH - Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology/genetics OTO - NOTNLM OT - B lymphoblastic leukemia OT - Cancer genetics OT - Next-generation sequencing OT - Pediatric acute myeloid leukemia COIS- Declaration of Competing Interest Matthew C. Hiemenz is an employee of Foundation Medicine, Inc., a wholly owned subsidiary of Roche Holdings Inc. and Roche Finance Ltd., and has an equity interest in an affiliate of these Roche entities. EDAT- 2021/02/12 06:00 MHDA- 2021/10/21 06:00 CRDT- 2021/02/11 20:17 PHST- 2020/09/13 00:00 [received] PHST- 2020/11/24 00:00 [revised] PHST- 2021/01/18 00:00 [accepted] PHST- 2021/02/12 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/02/11 20:17 [entrez] AID - S2210-7762(21)00007-7 [pii] AID - 10.1016/j.cancergen.2021.01.007 [doi] PST - ppublish SO - Cancer Genet. 2021 Jun;254-255:25-33. doi: 10.1016/j.cancergen.2021.01.007. Epub 2021 Jan 21.