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Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia.
- Source :
-
British journal of haematology [Br J Haematol] 2015 Nov; Vol. 171 (4), pp. 574-84. Date of Electronic Publication: 2015 Jul 24. - Publication Year :
- 2015
-
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.<br /> (© 2015 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)
- Subjects :
- Age of Onset
Aneuploidy
Base Sequence
Cell Cycle Proteins
Chromosomes, Human, Pair 11 ultrastructure
Chromosomes, Human, Pair 3 ultrastructure
DNA Methylation
DNA, Neoplasm genetics
DNA-Binding Proteins
Female
Fetal Diseases genetics
Gene Deletion
Gene Dosage
Genes, Neoplasm
Humans
In Situ Hybridization, Fluorescence
Infant
Infant, Newborn
Male
Molecular Sequence Data
Mutation
Polymorphism, Single Nucleotide
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma embryology
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma epidemiology
Promoter Regions, Genetic genetics
Proteins genetics
Sequence Deletion
Genotype
Neoplasm Proteins genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2141
- Volume :
- 171
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 26205622
- Full Text :
- https://doi.org/10.1111/bjh.13613