umu.sePublications
Change search
ReferencesLink to record
Permanent link

Direct link
The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes
Show others and affiliations
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 >= 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
Wiley-Blackwell, 2016. Vol. 174, no 2, 292-301 p.
Keyword [en]
paediatric acute myeloid leukaemia, single nucleotide polymorphism array, targeted deep exon sequencing
National Category
Hematology
Identifiers
URN: urn:nbn:se:umu:diva-126756DOI: 10.1111/bjh.14056ISI: 000383773700012PubMedID: 27022003OAI: oai:DiVA.org:umu-126756DiVA: diva2:1038389
Available from: 2016-10-18 Created: 2016-10-13 Last updated: 2016-10-18Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Forestier, Erik
By organisation
Department of Medical Biosciences
In the same journal
British Journal of Haematology
Hematology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 4 hits
ReferencesLink to record
Permanent link

Direct link