PMID- 32272434 OWN - NLM STAT- MEDLINE DCOM- 20200921 LR - 20200921 IS - 2210-7762 (Print) VI - 243 DP - 2020 May TI - Characterizing false-positive fluorescence in situ hybridization results by mate-pair sequencing in a patient with chronic myeloid leukemia and progression to myeloid blast crisis. PG - 48-51 LID - S2210-7762(20)30148-4 [pii] LID - 10.1016/j.cancergen.2020.02.008 [doi] AB - Traditional cytogenetic testing methodologies, including conventional chromosome analysis and fluorescence in situ hybridization (FISH), are invaluable for the detection or recurrent genetic abnormalities in various hematologic malignancies. However, technological advances, including a novel next-generation sequencing technique termed mate-pair sequencing (MPseq), continue to revolutionize the field of cytogenetics by enabling the characterization of structural variants at a significantly higher resolution compared to traditional methodologies. To illustrate the power of MPseq, we present a 27-year-old male diagnosed with chronic myeloid leukemia in myeloid blast crisis with multiple chromosomal abnormalities observed in all 20 metaphases from a peripheral blood specimen, including t(9;22)(q34;q11.2) and t(4;11)(q12;p15). Suspicious of a novel NUP98/PDGFRA fusion [t(4;11)(q12;p15)], break-apart FISH probe sets for the PDGFRA (4q12) and NUP98 (11p15.4) gene regions were performed and were both positive in approximately 86% of 200 interphase nuclei. However, subsequent MPseq testing revealed breakpoints located within the NUP98 gene and within an intergenic region (4q12) located between the CHIC2 and PDGFRA genes, indicating this 4;11 translocation does not result in the predicted NUP98/PDGFRA gene fusion as inferred from FISH and conventional chromosome results. This case demonstrates the clinical utility of MPseq, particularly for characterizing novel gene fusion events which may ultimately identify a false-positive FISH result. CI - Copyright (c) 2020. Published by Elsevier Inc. FAU - Lopes, Jaime L AU - Lopes JL AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. FAU - Webley, Matthew AU - Webley M AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. FAU - Pitel, Beth A AU - Pitel BA AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. FAU - Pearce, Kathryn E AU - Pearce KE AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. FAU - Smadbeck, James B AU - Smadbeck JB AD - Mayo Clinic, Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, MN, United States. FAU - Johnson, Sarah H AU - Johnson SH AD - Mayo Clinic, Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, MN, United States. FAU - Vasmatzis, George AU - Vasmatzis G AD - Mayo Clinic, Center for Individualized Medicine-Biomarker Discovery, Mayo Clinic, Rochester, MN, United States. FAU - Sukov, William R AU - Sukov WR AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. FAU - Greipp, Patricia T AU - Greipp PT AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. FAU - Hoppman, Nicole L AU - Hoppman NL AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. FAU - Ketterling, Rhett P AU - Ketterling RP AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. FAU - Baughn, Linda B AU - Baughn LB AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. FAU - Finn, Laura AU - Finn L AD - Division of Hematology and Bone Marrow Transplant, Department of Internal Medicine, Ochsner Medical Center, New Orleans, LA, United States. FAU - Peterson, Jess F AU - Peterson JF AD - Mayo Clinic, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Rochester, MN, United States. Electronic address: peterson.jess@mayo.edu. LA - eng PT - Case Reports PT - Journal Article DEP - 20200317 PL - United States TA - Cancer Genet JT - Cancer genetics JID - 101539150 RN - 0 (Nuclear Pore Complex Proteins) RN - 0 (Nup98 protein, human) RN - 0 (Oncogene Proteins, Fusion) RN - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha) SB - IM MH - Adult MH - Blast Crisis/diagnosis/*genetics MH - Chromosome Aberrations MH - Chromosomes, Human, Pair 11/genetics MH - Chromosomes, Human, Pair 22/genetics MH - Chromosomes, Human, Pair 4/genetics MH - Chromosomes, Human, Pair 9/genetics MH - Cytogenetic Analysis MH - Disease Progression MH - False Positive Reactions MH - *High-Throughput Nucleotide Sequencing MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics MH - Male MH - Nuclear Pore Complex Proteins/genetics MH - Oncogene Proteins, Fusion/genetics/*isolation & purification MH - Receptor, Platelet-Derived Growth Factor alpha/genetics OTO - NOTNLM OT - Chronic myeloid leukemia (CML) OT - Conventional chromosome analysis OT - Fluorescence in situ hybridization (FISH) OT - Mate-pair sequencing (MPseq) COIS- Declaration of Competing Interest None EDAT- 2020/04/10 06:00 MHDA- 2020/09/22 06:00 CRDT- 2020/04/10 06:00 PHST- 2019/11/19 00:00 [received] PHST- 2020/01/23 00:00 [revised] PHST- 2020/02/27 00:00 [accepted] PHST- 2020/04/10 06:00 [pubmed] PHST- 2020/09/22 06:00 [medline] PHST- 2020/04/10 06:00 [entrez] AID - S2210-7762(20)30148-4 [pii] AID - 10.1016/j.cancergen.2020.02.008 [doi] PST - ppublish SO - Cancer Genet. 2020 May;243:48-51. doi: 10.1016/j.cancergen.2020.02.008. Epub 2020 Mar 17.