title: Genomic imbalances associated with secondary acute leukemias in Hodgkin lymphoma.
abstract: Secondary tumors and leukemias are major complications in Hodgkin lymphoma (HL). They likely arise from clonal selection of cells that have accumulated genomic lesions induced by chemo- and radiotherapy and may be further promoted by the loss of DNA repair and/or other pathways ensuring the fidelity of replicated DNA. To distinguish genomic imbalances associated with the development of acute myeloid leukemia (AML) in HL we used an array-based comparative genomic hybridization (aCGH) strategy on whole lymph node biopsies of HL patient. Genomic imbalances (amplifications and deletions) associated with AML outcome in 3 classic HL patients, at clinical diagnosis they exhibited a discrete individual variability. Three amplifications and 5 deletions were shared by all 3 patients. They involved AFM137XA11, a 9p11.2 pericentric region; FGFR1, the FGF receptor most frequently translocated in AML; PPARBP, a co-activator of nuclear receptors RARalpha, RXR and TRbeta1; AFM217YD10, a 17q25 telomeric region; FGR, an SRC2 kinase involved in cytokine production by NK and CD4+ NKT cells; GATA3, a Th2-specific transcription factor; TOP1, involved in DNA recombination and repair; WT1, a transcription factor involved in CD8+ T cell response against leukaemic blasts. Immunohistochemistry confirmed aCGH results and distinguished the distribution of either amplified or deleted gene products in neoplastic Reed Sternberg (RS) cells and non-neoplastic lymph node components.
authors.affiliation: Istituto di Ematologia e Oncologia Medica Lorenzo e Ariosto Seràgnoli, Università di Bologna - Medical School, 40138 Bologna, Italy. gbrusa@alma.unibo.it
authors.forename: Gianluca
authors.initials: G
authors.lastname: Brusa
authors.forename: Elisa
authors.initials: E
authors.lastname: Zuffa
authors.forename: Claudia Maria
authors.initials: CM
authors.lastname: Hattinger
authors.forename: Massimo
authors.initials: M
authors.lastname: Serra
authors.forename: Daniel
authors.initials: D
authors.lastname: Remondini
authors.forename: Gastone
authors.initials: G
authors.lastname: Castellani
authors.forename: Simona
authors.initials: S
authors.lastname: Righi
authors.forename: Cristina
authors.initials: C
authors.lastname: Campidelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Pileri
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Zinzani
authors.forename: Annalisa
authors.initials: A
authors.lastname: Gabriele
authors.forename: Manuela
authors.initials: M
authors.lastname: Mancini
authors.forename: Patrizia
authors.initials: P
authors.lastname: Corrado
authors.forename: Enza
authors.initials: E
authors.lastname: Barbieri
authors.forename: Maria Alessandra
authors.initials: MA
authors.lastname: Santucci
mesh_terms: D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004260:DNA Repair; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D017353:Gene Deletion; D042822:Genomic Instability; D006689:Hodgkin Disease / Q000150:complications / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D000071447:N-Myc Proto-Oncogene Protein; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins