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

作     者：Olsson, Linda Zettermark, Sofia Biloglav, Andrea Castor, Anders Behrendtz, Mikael Forestier, Erik Paulsson, Kajsa Johansson, Bertil 

作者机构：Lund Univ Div Clin Genet Dept Lab Med Lund Sweden Dept Clin Genet Div Lab Med Off Med Serv Lund Sweden Skane Univ Hosp Dept Paediat Lund Sweden Linkoping Univ Hosp Dept Paediat Linkoping Sweden Umea Univ Dept Med Biosci Umea Sweden 

出 版 物：《BRITISH JOURNAL OF HAEMATOLOGY》 (英国血液学杂志)

年 卷 期：2016年第174卷第2期

页      面：292-301页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：Swedish Cancer Society Swedish Childhood Cancer Foundation Crafoord foundation Swedish Research Council Governmental Funding of Clinical Research within the National Health Service 

主　　题：paediatric acute myeloid leukaemia single nucleotide polymorphism array targeted deep exon sequencing 

摘      要：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.