The silent mutational landscape of infant MLL-AF4 pro-B acute lymphoblastic leukemia.
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Over 90% of infants (< 1-year-old) diagnosed with leukemia have pro-B acute lymphoblastic leukemia (ALL) containing the MLL-AF4 fusion. When compared with other forms of paediatric ALL affecting later B-cell differentiation, MLL-AF4 pro-B is associated with a dismal prognosis with a typical 5-year disease-free survival of <20%. MLL-AF4 may be sufficient on its own for leukemogenesis or the gene-fusion product may alternatively predispose transformed cells to global genetic instability, enhancing the acquisition of additional key mutations. To gain insight into the genomic landscape of infant MLL-AF4 pro-B ALL we performed whole genome sequencing of diagnostic leukemic blasts and matched germline samples from three MLL-AF4 pro-B ALL infants. Our analysis revealed few somatic changes (copy number abnormalities, loss of heterozygosity, or single nucleotide variants), demonstrating that only a very small number of mutations are necessary to generate infant MLL-leukemia.
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Oncogene Proteins, Fusion
Sequence Analysis, DNA
DNA Mutational Analysis
Loss of Heterozygosity
Polymorphism, Single Nucleotide
Myeloid-Lymphoid Leukemia Protein
Precursor Cell Lymphoblastic Leukemia-Lymphoma
DNA Copy Number Variations
Biology of Childhood Leukaemia
Molecular & Population Genetics
Genes, chromosomes & cancer, 2013, 52 (10), pp. 954 - 960