title: Refinement of IKZF1 recombination hotspots in pediatric BCP-ALL patients.
abstract: Chromosomal translocations resulting in chimeric fusion genes are prototypic for pediatric leukemia patients. The most known fusions are ETV6-RUNX1 or BCR-ABL1 in B-cell progenitor (BCP)-ALL, and rearrangements of MLL in pediatric ALL and AML. Genome-wide sequencing projects have revealed additional, recurrent gene mutations in B cell malignancies. One of these mutations comprises the IKZF1 gene, encoding the IKAROS transcription factor which is one of the essential transcription factors driving lymphoid development. IKZF1 deletions were first identified by SNP arrays in ALL patients, and later identified with a high prevalence in BCR-ABL1(+) patients. IKZF1 deletions turned out to be an independent prognostic marker associated with a poor outcome. Here, we characterized IKZF1 deletions in pediatric BCP-ALL patients by combining MLPA mapping experiments with long distance inverse PCR. The aim of our study was also to compare existing methods with our approach. Our attempt confirmed many of the existing data but revealed a more complex pattern of recombination sites, including a total of 4 recombination hotspots. This extended knowledge was translated into a novel, multiplex PCR assay that allows to perform IKZF1 deletion analyses by using a 2-tube PCR approach.
authors.affiliation: Institute of Pharmaceutical Biology/ZAFES, Goethe-University of Frankfurt, Biocenter Max-von-Laue-Str. 9, D-60438 Frankfurt/Main, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Udo
authors.initials: U
authors.lastname: Zur Stadt
authors.forename: Gabriele
authors.initials: G
authors.lastname: Escherich
authors.forename: Julia
authors.initials: J
authors.lastname: Hofmann
authors.forename: Renata
authors.initials: R
authors.lastname: Binato
authors.forename: Thayana Conceição
authors.initials: TC
authors.lastname: Barbosa
authors.forename: Mariana
authors.initials: M
authors.lastname: Emerenciano
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pombo-de-Oliveira
authors.forename: Martin
authors.initials: M
authors.lastname: Horstmann
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
keywords: Childhood leukemia; IKAROS; IKZF1; cancer genetics; gene deletion; leukemia markers