title: Detailed gene dose analysis reveals recurrent focal gene deletions in pediatric B-cell precursor acute lymphoblastic leukemia.
abstract: To identify copy number alterations (CNAs) in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL), array comparative genomic hybridization was performed on 50 cases; detected CNAs were validated in a cohort of 191 cases analyzed by single nucleotide polymorphism arrays. Apart from CNAs involving leukemia-associated genes, recurrent deletions targeting genes not previously implicated in BCP ALL, e.g. INIP, IRF1 and PDE4B, were identified. Deletions of the DNA repair gene INIP were exclusively found in cases with t(12;21), and deletions of SH2B3 were associated with intrachromosomal amplification of chromosome 21 (p < 0.001). A majority of BTLA deletions (7/11; 64%) affected samples with gain of 21q chromosome material, suggesting that BTLA deletions are associated with both germline and somatic gain of chromosome 21. In cases without known risk-associated cytogenetic markers, CNAs associated with adverse prognosis were identified in 50% (10/20), indicating that a majority of these cases could be assigned to distinct genetic subtypes.
authors.affiliation: a Department of Molecular Medicine and Surgery , Center for Molecular Medicine, Karolinska Institutet , Stockholm , Sweden ;
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Ivanov Öfverholm
authors.affiliation: a Department of Molecular Medicine and Surgery , Center for Molecular Medicine, Karolinska Institutet , Stockholm , Sweden ;
authors.forename: Anh Nhi
authors.initials: AN
authors.lastname: Tran
authors.affiliation: b Division of Clinical Genetics, Department of Laboratory Medicine , Lund University , Lund , Sweden ;
authors.forename: Linda
authors.initials: L
authors.lastname: Olsson
authors.affiliation: a Department of Molecular Medicine and Surgery , Center for Molecular Medicine, Karolinska Institutet , Stockholm , Sweden ;
authors.forename: Vasilios
authors.initials: V
authors.lastname: Zachariadis
authors.affiliation: c Department of Women's and Children's Health , Karolinska Institutet , Stockholm , Sweden ;
authors.forename: Mats
authors.initials: M
authors.lastname: Heyman
authors.affiliation: a Department of Molecular Medicine and Surgery , Center for Molecular Medicine, Karolinska Institutet , Stockholm , Sweden ;
authors.forename: Eva
authors.initials: E
authors.lastname: Rudd
authors.affiliation: a Department of Molecular Medicine and Surgery , Center for Molecular Medicine, Karolinska Institutet , Stockholm , Sweden ;
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Syk Lundberg
authors.affiliation: a Department of Molecular Medicine and Surgery , Center for Molecular Medicine, Karolinska Institutet , Stockholm , Sweden ;
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
authors.affiliation: b Division of Clinical Genetics, Department of Laboratory Medicine , Lund University , Lund , Sweden ;|d Department of Clinical Genetics , University and Regional Laboratories , Region Skåne , Lund , Sweden.
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
authors.affiliation: a Department of Molecular Medicine and Surgery , Center for Molecular Medicine, Karolinska Institutet , Stockholm , Sweden ;
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.affiliation: a Department of Molecular Medicine and Surgery , Center for Molecular Medicine, Karolinska Institutet , Stockholm , Sweden ;
authors.forename: Gisela
authors.initials: G
authors.lastname: Barbany
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D018450:Disease Progression; D044127:Epigenesis, Genetic; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D012008:Recurrence
keywords: B-Other; CNA; copy number; deletion; pediatric ALL