Amplification and translocation of 3q26 with overexpression of EVI1 in Fanconi anemia-derived childhood acute myeloid leukemia with biallelic FANCD1/BRCA2 disruption.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72886
Title:
Amplification and translocation of 3q26 with overexpression of EVI1 in Fanconi anemia-derived childhood acute myeloid leukemia with biallelic FANCD1/BRCA2 disruption.
Authors:
Meyer, Stefan; Fergusson, William D; Whetton, Anthony D; Moreira-Leite, Flavia; Pepper, Stuart D; Miller, Crispin J; Saunders, Emma K; White, Daniel J; Will, Andrew M; Eden, Tim O B; Ikeda, Hideyuki; Ullmann, Reinhard; Tuerkmen, Seval; Gerlach, Antje; Klopocki, Eva; Tönnies, Holger
Abstract:
Fanconi anemia (FA) is an inherited disease with congenital abnormalities and an extreme risk of acute myeloid leukemia (AML). Genetic events occurring during malignant transformation in FA and the biology of FA-associated AML are poorly understood, but are often preceded by the development of chromosomal aberrations involving 3q26-29 in bone marrow of FA patients. We report here the molecular cytogenetic characterization of FA-derived AML cell lines SB1685CB and SB1690CB by conventional and array comparative genomic hybridization, fluorescence in situ hybridization, and SKY. We identified gains of a 3.7 MB chromosomal region on 3q26.2-26.31, which preceded transformation to overt leukemia. This region harbors the oncogenic transcription factor EVI1. A third FA-derived cell line, FA-AML1, carried a translocation with ectopic localization of 3q26 including EVI1. Rearrangements of 3q, which are rare in childhood AML, commonly result in overexpression of EVI1, which determines specific gene expression patterns and confers poor prognosis. We detected overexpression of EVI1 in all three FA-derived AML. Our results suggest a link between the FA defect, chromosomal aberrations involving 3q and overexpression of EVI1. We hypothesize that constitutional or acquired FA defects might be a common factor for the development of 3q abnormalities in AML. In addition, cryptic imbalances as detected here might account for overexpression of EVI1 in AML without overt 3q26 rearrangements.
Affiliation:
Academic Unit of Paediatric Oncology, Christie Hospital Trust, University of anchester, Manchester, UK. stefan.meyer@manchester.ac.uk
Citation:
Amplification and translocation of 3q26 with overexpression of EVI1 in Fanconi anemia-derived childhood acute myeloid leukemia with biallelic FANCD1/BRCA2 disruption. 2007, 46 (4):359-72 Genes Chromosomes Cancer
Journal:
Genes, Chromosomes & Cancer
Issue Date:
Apr-2007
URI:
http://hdl.handle.net/10541/72886
DOI:
10.1002/gcc.20417
PubMed ID:
17243162
Type:
Article
Language:
en
ISSN:
1045-2257
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMeyer, Stefan-
dc.contributor.authorFergusson, William D-
dc.contributor.authorWhetton, Anthony D-
dc.contributor.authorMoreira-Leite, Flavia-
dc.contributor.authorPepper, Stuart D-
dc.contributor.authorMiller, Crispin J-
dc.contributor.authorSaunders, Emma K-
dc.contributor.authorWhite, Daniel J-
dc.contributor.authorWill, Andrew M-
dc.contributor.authorEden, Tim O B-
dc.contributor.authorIkeda, Hideyuki-
dc.contributor.authorUllmann, Reinhard-
dc.contributor.authorTuerkmen, Seval-
dc.contributor.authorGerlach, Antje-
dc.contributor.authorKlopocki, Eva-
dc.contributor.authorTönnies, Holger-
dc.date.accessioned2009-07-07T16:30:14Z-
dc.date.available2009-07-07T16:30:14Z-
dc.date.issued2007-04-
dc.identifier.citationAmplification and translocation of 3q26 with overexpression of EVI1 in Fanconi anemia-derived childhood acute myeloid leukemia with biallelic FANCD1/BRCA2 disruption. 2007, 46 (4):359-72 Genes Chromosomes Canceren
dc.identifier.issn1045-2257-
dc.identifier.pmid17243162-
dc.identifier.doi10.1002/gcc.20417-
dc.identifier.urihttp://hdl.handle.net/10541/72886-
dc.description.abstractFanconi anemia (FA) is an inherited disease with congenital abnormalities and an extreme risk of acute myeloid leukemia (AML). Genetic events occurring during malignant transformation in FA and the biology of FA-associated AML are poorly understood, but are often preceded by the development of chromosomal aberrations involving 3q26-29 in bone marrow of FA patients. We report here the molecular cytogenetic characterization of FA-derived AML cell lines SB1685CB and SB1690CB by conventional and array comparative genomic hybridization, fluorescence in situ hybridization, and SKY. We identified gains of a 3.7 MB chromosomal region on 3q26.2-26.31, which preceded transformation to overt leukemia. This region harbors the oncogenic transcription factor EVI1. A third FA-derived cell line, FA-AML1, carried a translocation with ectopic localization of 3q26 including EVI1. Rearrangements of 3q, which are rare in childhood AML, commonly result in overexpression of EVI1, which determines specific gene expression patterns and confers poor prognosis. We detected overexpression of EVI1 in all three FA-derived AML. Our results suggest a link between the FA defect, chromosomal aberrations involving 3q and overexpression of EVI1. We hypothesize that constitutional or acquired FA defects might be a common factor for the development of 3q abnormalities in AML. In addition, cryptic imbalances as detected here might account for overexpression of EVI1 in AML without overt 3q26 rearrangements.en
dc.language.isoenen
dc.subjectLeukaemia, Myeloiden
dc.subject.meshAcute Disease-
dc.subject.meshBRCA2 Protein-
dc.subject.meshCell Line-
dc.subject.meshChild-
dc.subject.meshChromosomes, Human, Pair 3-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFanconi Anemia-
dc.subject.meshGene Amplification-
dc.subject.meshHumans-
dc.subject.meshLeukemia, Myeloid-
dc.subject.meshProto-Oncogenes-
dc.subject.meshTranscription Factors-
dc.subject.meshTranslocation, Genetic-
dc.titleAmplification and translocation of 3q26 with overexpression of EVI1 in Fanconi anemia-derived childhood acute myeloid leukemia with biallelic FANCD1/BRCA2 disruption.en
dc.typeArticleen
dc.contributor.departmentAcademic Unit of Paediatric Oncology, Christie Hospital Trust, University of anchester, Manchester, UK. stefan.meyer@manchester.ac.uken
dc.identifier.journalGenes, Chromosomes & Canceren

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