The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes

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Bibtex

@article{a92e294e01954e8fad9881e2dad79722,
title = "The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes",
abstract = "Cytogenetic analyses of a consecutive series of 67 paediatric (median age 8 years; range 0-17) de novo acute myeloid leukaemia (AML) patients revealed aberrations in 55 (82{\%}) cases. The most common subgroups were KMT2A rearrangement (29{\%}), normal karyotype (15{\%}), RUNX1-RUNX1T1 (10{\%}), deletions of 5q, 7q and/or 17p (9{\%}), myeloid leukaemia associated with Down syndrome (7{\%}), PML-RARA (7{\%}) and CBFB-MYH11 (5{\%}). Single nucleotide polymorphism array (SNP-A) analysis and exon sequencing of 100 genes, performed in 52 and 40 cases, respectively (39 overlapping), revealed ≥1 aberration in 89{\%}; when adding cytogenetic data, this frequency increased to 98{\%}. Uniparental isodisomies (UPIDs) were detected in 13{\%} and copy number aberrations (CNAs) in 63{\%} (median 2/case); three UPIDs and 22 CNAs were recurrent. Twenty-two genes were targeted by focal CNAs, including AEBP2 and PHF6 deletions and genes involved in AML-associated gene fusions. Deep sequencing identified mutations in 65{\%} of cases (median 1/case). In total, 60 mutations were found in 30 genes, primarily those encoding signalling proteins (47{\%}), transcription factors (25{\%}), or epigenetic modifiers (13{\%}). Twelve genes (BCOR, CEBPA, FLT3, GATA1, KIT, KRAS, NOTCH1, NPM1, NRAS, PTPN11, SMC3 and TP53) were recurrently mutated. We conclude that SNP-A and deep sequencing analyses complement the cytogenetic diagnosis of paediatric AML.",
author = "Linda Olsson and Sofia Zettermark and Andrea Biloglav and Anders Castor and Mikael Behrendtz and Erik Forestier and Kajsa Paulsson and Bertil Johansson",
note = "{\circledC} 2016 John Wiley & Sons Ltd.",
year = "2016",
month = "7",
doi = "10.1111/bjh.14056",
language = "English",
volume = "174",
pages = "292--301",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Federation of European Neuroscience Societies and Blackwell Publishing Ltd",
number = "2",

}