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The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes
Lund University, Sweden; Department Clin Genet, Sweden.
Lund University, Sweden.
Lund University, Sweden.
Skåne University Hospital, Sweden.
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2016 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 174, no 2, 292-301 p.Article in journal (Refereed) Published
Abstract [en]

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 CBFBMYH11 (5%). Single nucleotide polymorphism array (SNP-A) analysis and exon sequencing of 100 genes, performed in 52 and 40 cases, respectively (39 overlapping), revealed amp;gt;= 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.

Place, publisher, year, edition, pages
Chichester: WILEY-BLACKWELL , 2016. Vol. 174, no 2, 292-301 p.
Keyword [en]
paediatric acute myeloid leukaemia; single nucleotide polymorphism array; targeted deep exon sequencing
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URN: urn:nbn:se:liu:diva-132083DOI: 10.1111/bjh.14056ISI: 000383773700012PubMedID: 27022003OAI: diva2:1038377

Funding Agencies|Swedish Cancer Society; Swedish Childhood Cancer Foundation; Crafoord foundation; Swedish Research Council; Governmental Funding of Clinical Research within the National Health Service

Available from: 2016-10-18 Created: 2016-10-17 Last updated: 2016-10-27Bibliographically approved

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Behrendtz, Mikael
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Department of Paediatrics in Linköping
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