title: MYC amplification in multiple marker chromosomes and EZH2 microdeletion in a man with acute myeloid leukemia.
abstract: The role of MYC and EZH2 in acute myeloid leukemia (AML) pathogenesis is poorly understood. Herein we present a case of AML with MYC amplification in marker chromosomes and a microdeletion of chromosome 7 below cytogenetic resolution. The karyotype of the patient's bone marrow aspirate showed three to five marker chromosomes in all dividing cells without other structural or numerical chromosomal abnormalities. Analysis by fluorescence in situ hybridization (FISH) with a probe specific for the human MYC gene revealed amplification of the oncogene localized to the marker chromosomes. Using whole genome single nucleotide polymorphism (SNP) microarray analysis, an approximately 4.4 Mb amplicon containing the MYC gene was identified with an estimated amplification of about 30 copies per leukemic cell and, thus, an average of about 8 copies per marker chromosome. A 6.4 Mb hemizygous microdeletion of chromosome 7 within band q36.1 was also found by SNP microarray analysis in a cellular-equivalent dosage of 50%. The microdeletion spans multiple genes, including EZH2, a gene with well-known cancer association. No mutation was found in the remaining EZH2 allele by next generation gene sequencing. The combination of MYC amplification and EZH2 deletion, which has not been described previously in AML, may suggest a synergistic role of the two oncogenes in the pathogenesis of the patient's acute leukemia.
authors: Division of Hematology and Oncology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Hematology and Oncology, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. Electronic address: zxiang@uams.edu.
authors: Zhifu
authors: Z
authors: Xiang
authors: Division of Hematology and Oncology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: Al-Ola
authors: AO
authors: Abdallah
authors: Division of Hematology and Oncology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Hematology and Oncology, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors: Rangaswamy
authors: R
authors: Govindarajan
authors: Division of Hematology and Oncology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Division of Hematology and Oncology, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors: Paulette
authors: P
authors: Mehta
authors: Division of Hematology and Oncology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors: Peter D
authors: PD
authors: Emanuel
authors: Division of Cytogenetics, LabCorp, Center for Molecular Biology and Pathology, Research Triangle Park, NC, USA.
authors: Peter
authors: P
authors: Papenhausen
authors: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Pathology and Laboratory Medicine Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors: Steven A
authors: SA
authors: Schichman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000071221:Enhancer of Zeste Homolog 2 Protein; D005784:Gene Amplification; D017353:Gene Deletion; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics*; D008297:Male; D063151:Polycomb Repressive Complex 2 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
keywords: Acute myeloid leukemia; EZH2; Genetic abnormality; MYC; Marker chromosomes