PMID- 36417763 OWN - NLM STAT- MEDLINE DCOM- 20230405 LR - 20240316 IS - 2473-9537 (Electronic) IS - 2473-9529 (Print) IS - 2473-9529 (Linking) VI - 7 IP - 7 DP - 2023 Apr 11 TI - Optical genome mapping in acute myeloid leukemia: a multicenter evaluation. PG - 1297-1307 LID - 10.1182/bloodadvances.2022007583 [doi] AB - Detection of hallmark genomic aberrations in acute myeloid leukemia (AML) is essential for diagnostic subtyping, prognosis, and patient management. However, cytogenetic/cytogenomic techniques used to identify those aberrations, such as karyotyping, fluorescence in situ hybridization (FISH), or chromosomal microarray analysis (CMA), are limited by the need for skilled personnel as well as significant time, cost, and labor. Optical genome mapping (OGM) provides a single, cost-effective assay with a significantly higher resolution than karyotyping and with a comprehensive genome-wide analysis comparable with CMA and the added unique ability to detect balanced structural variants (SVs). Here, we report in a real-world setting the performance of OGM in a cohort of 100 AML cases that were previously characterized by karyotype alone or karyotype and FISH or CMA. OGM identified all clinically relevant SVs and copy number variants (CNVs) reported by these standard cytogenetic methods when representative clones were present in >5% allelic fraction. Importantly, OGM identified clinically relevant information in 13% of cases that had been missed by the routine methods. Three cases reported with normal karyotypes were shown to have cryptic translocations involving gene fusions. In 4% of cases, OGM findings would have altered recommended clinical management, and in an additional 8% of cases, OGM would have rendered the cases potentially eligible for clinical trials. The results from this multi-institutional study indicate that OGM effectively recovers clinically relevant SVs and CNVs found by standard-of-care methods and reveals additional SVs that are not reported. Furthermore, OGM minimizes the need for labor-intensive multiple cytogenetic tests while concomitantly maximizing diagnostic detection through a standardized workflow. CI - (c) 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. FAU - Levy, Brynn AU - Levy B AUID- ORCID: 0000-0002-4213-3480 AD - Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY. FAU - Baughn, Linda B AU - Baughn LB AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. FAU - Akkari, Yassmine AU - Akkari Y AD - Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH. FAU - Chartrand, Scott AU - Chartrand S AD - Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA. FAU - LaBarge, Brandon AU - LaBarge B AD - Department of Otolaryngology, Penn State College of Medicine, Hershey, PA. FAU - Claxton, David AU - Claxton D AUID- ORCID: 0000-0001-9209-2405 AD - Department of Hematology and Oncology, Department of Medicine, Penn State College of Medicine, Hershey, PA. FAU - Lennon, P Alan AU - Lennon PA AD - PathGroup, Nashville, TN. FAU - Cujar, Claudia AU - Cujar C AUID- ORCID: 0000-0003-2278-7839 AD - Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY. FAU - Kolhe, Ravindra AU - Kolhe R AUID- ORCID: 0000-0002-8283-2403 AD - Department of Pathology, Medical College of Georgia at Augusta University, Augusta, GA. FAU - Kroeger, Kate AU - Kroeger K AD - Cytogenetics Laboratory, Seattle Cancer Care Alliance, Seattle, WA. FAU - Pitel, Beth AU - Pitel B AUID- ORCID: 0000-0002-5138-824X AD - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. FAU - Sahajpal, Nikhil AU - Sahajpal N AD - Department of Pathology, Medical College of Georgia at Augusta University, Augusta, GA. FAU - Sathanoori, Malini AU - Sathanoori M AD - PathGroup, Nashville, TN. FAU - Vlad, George AU - Vlad G AD - Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY. FAU - Zhang, Lijun AU - Zhang L AUID- ORCID: 0000-0003-4974-2745 AD - Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA. FAU - Fang, Min AU - Fang M AD - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA. FAU - Kanagal-Shamanna, Rashmi AU - Kanagal-Shamanna R AUID- ORCID: 0000-0001-7829-5249 AD - Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX. FAU - Broach, James R AU - Broach JR AUID- ORCID: 0000-0003-1197-0312 AD - Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA. LA - eng GR - P01 CA171983/CA/NCI NIH HHS/United States PT - Journal Article PT - Multicenter Study PL - United States TA - Blood Adv JT - Blood advances JID - 101698425 SB - IM MH - Humans MH - *Chromosome Aberrations MH - In Situ Hybridization, Fluorescence MH - *Leukemia, Myeloid, Acute/diagnosis/genetics MH - Karyotype MH - Chromosome Mapping PMC - PMC10119592 COIS- Conflict-of-interest disclosure: The authors declare no competing financial interests. EDAT- 2022/11/24 06:00 MHDA- 2023/04/05 06:42 PMCR- 2022/11/25 CRDT- 2022/11/23 17:02 PHST- 2022/11/05 00:00 [accepted] PHST- 2022/03/14 00:00 [received] PHST- 2023/04/05 06:42 [medline] PHST- 2022/11/24 06:00 [pubmed] PHST- 2022/11/23 17:02 [entrez] PHST- 2022/11/25 00:00 [pmc-release] AID - 493328 [pii] AID - 10.1182/bloodadvances.2022007583 [doi] PST - ppublish SO - Blood Adv. 2023 Apr 11;7(7):1297-1307. doi: 10.1182/bloodadvances.2022007583.