title: The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia.
abstract: High hyperdiploid (51-67 chromosomes) acute lymphoblastic leukemia (ALL) is one of the most common childhood malignancies, comprising 30% of all pediatric B cell-precursor ALL. Its characteristic genetic feature is the nonrandom gain of chromosomes X, 4, 6, 10, 14, 17, 18 and 21, with individual trisomies or tetrasomies being seen in over 75% of cases, but the pathogenesis remains poorly understood. We performed whole-genome sequencing (WGS) (n = 16) and/or whole-exome sequencing (WES) (n = 39) of diagnostic and remission samples from 51 cases of high hyperdiploid ALL to further define the genomic landscape of this malignancy. The majority of cases showed involvement of the RTK-RAS pathway and of histone modifiers. No recurrent fusion gene-forming rearrangement was found, and an analysis of mutations on trisomic chromosomes indicated that the chromosomal gains were early events, strengthening the notion that the high hyperdiploid pattern is the main driver event in this common pediatric malignancy.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
authors.forename: Kajsa
authors.identifier: 000000017950222X
authors.initials: K
authors.lastname: Paulsson
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
authors.forename: Henrik
authors.identifier: 0000000187031173
authors.initials: H
authors.lastname: Lilljebjörn
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biloglav
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Olsson
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Rissler
authors.affiliation: Department of Pediatrics, Skåne University Hospital, Lund University, Lund, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Castor
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gisela
authors.initials: G
authors.lastname: Barbany
authors.affiliation: 1] Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden. [2] Laboratory of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Fogelstrand
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Nordgren
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Helene
authors.initials: H
authors.lastname: Sjögren
authors.affiliation: 1] Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden. [2] Department of Clinical Genetics, University and Regional Laboratories Region Skåne, Lund, Sweden.
authors.forename: Thoas
authors.initials: T
authors.lastname: Fioretos
authors.affiliation: 1] Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden. [2] Department of Clinical Genetics, University and Regional Laboratories Region Skåne, Lund, Sweden.
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004171:Diploidy; D005260:Female; D015894:Genome, Human; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*