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Amplification and translocation of 3q26 with overexpression of EVI1 in Fanconi anemia‐derived childhood acute myeloid leukemia with biallelic FANCD1 / BRCA2 disruption
Author(s) -
Meyer Stefan,
Fergusson William D.,
Whetton Anthony D.,
MoreiraLeite Flavia,
Pepper Stuart D.,
Miller Crispin,
Saunders Emma K.,
White Daniel J.,
Will Andrew M.,
Eden Tim,
Ikeda Hideyuki,
Ullmann Reinhard,
Tuerkmen Seval,
Gerlach Antje,
Klopocki Eva,
Tönnies Holger
Publication year - 2007
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20417
Subject(s) - myeloid leukemia , fanconi anemia , chromosomal translocation , biology , cancer research , comparative genomic hybridization , myeloid , fluorescence in situ hybridization , ectopic expression , leukemia , genetics , gene , microbiology and biotechnology , dna repair , chromosome
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. © 2007 Wiley‐Liss, Inc.