title: Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia.
abstract: Infant T-cell acute lymphoblastic leukaemia (iT-ALL) is a very rare and poorly defined entity with a poor prognosis. We assembled a unique series of 13 infants with T-ALL, which allowed us to identify genotypic abnormalities and to investigate prenatal origins. Matched samples (diagnosis/remission) were analysed by single nucleotide polymorphism-array to identify genomic losses and gains. In three cases, we identified a recurrent somatic deletion on chromosome 3. These losses result in the complete deletion of MLF1 and have not previously been described in T-ALL. We observed two cases with an 11p13 deletion (LMO2-related), one of which also harboured a deletion of RB1. Another case presented a large 11q14·1-11q23·2 deletion that included ATM and only five patients (38%) showed deletions of CDKN2A/B. Four cases showed NOTCH1 mutations; in one case FBXW7 was the sole mutation and three cases showed alterations in PTEN. KMT2A rearrangements (KMT2A-r) were detected in three out of 13 cases. For three patients, mutations and copy number alterations (including deletion of PTEN) could be backtracked to birth using neonatal blood spot DNA, demonstrating an in utero origin. Overall, our data indicates that iT-ALL has a diverse but distinctive profile of genotypic abnormalities when compared to T-ALL in older children and adults.
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.|Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Marcela B
authors.initials: MB
authors.lastname: Mansur
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
authors.forename: Frederik W
authors.initials: FW
authors.lastname: van Delft
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Colman
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Furness
authors.affiliation: Centre for Biological Sciences, University of Southampton, Southampton, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Emerenciano
authors.affiliation: Paediatric Malignancy Cytogenetics Unit, Institute of Child Health & Great Ormond Street Hospital, London, UK.
authors.forename: Helena
authors.initials: H
authors.lastname: Kempski
authors.affiliation: Department of Genetics, Robert Debré Hospital, APHP, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Clappier
authors.affiliation: Department of Genetics, Robert Debré Hospital, APHP, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Cave
authors.affiliation: Haematology Laboratory, Saint-Louis Louis Hospital, APHP, Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.affiliation: Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Pombo-de-Oliveira
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
authors.forename: Mel
authors.initials: M
authors.lastname: Greaves
authors.affiliation: Centre for Evolution and Cancer, The Institute of Cancer Research, London, UK.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Ford
mesh_terms: D017668:Age of Onset; D000782:Aneuploidy; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure; D002893:Chromosomes, Human, Pair 3 / Q000648:ultrastructure; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005315:Fetal Diseases / Q000235:genetics; D017353:Gene Deletion; D018628:Gene Dosage; D052138:Genes, Neoplasm; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000196:embryology / Q000453:epidemiology / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics; D017384:Sequence Deletion
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C100852:MLF1 protein, human; D009363:Neoplasm Proteins; D011506:Proteins
keywords: CNAs and in utero origin; T-cell acute lymphoblastic leukaemia; genomic profile; infant