Genomic profiling of acute myeloid leukaemia associated with ataxia telangiectasia identifies a complex karyotype with wild-type TP53 and mutant KRAS, G3BP1 and IL7R.
Arkwright, Peter D
Taylor, A Malcolm R
Pediatric blood & cancer
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Goldgraben, M., Fewings, E., Larionov, A., Scarth, J., Redman, J., Telford, N., Arkwright, P. D., et al. (2020). Genomic profiling of acute myeloid leukaemia associated with ataxia telangiectasia identifies a complex karyotype with wild-type TP53 and mutant KRAS, G3BP1 and IL7R.. Pediatric blood & cancer, 67 (9), e28354. https://doi.org/10.1002/pbc.28354
Ataxia Telangiectasia (A-T) is an autosomal recessive disease, characterised by progressive neurodegeneration with cerebellar ataxia, oculo-cutaneous telangiectasia, immunodeficiency and cancer predisposition. It is caused by biallelic mutations in ATM (Ataxia Telangiectasia Mutated, chromosome 11q22.3) encoding a serine/threonine kinase essential in cell cycle control, DNA double-strand break repair and haematopoietic stem cell maintenance 1,2. Individuals with A-T classically develop lymphoid malignancies, a broad spectrum of other malignancies 3 and rarely, acute myeloid leukaemia (AML) 4-7. Previous AT-AML reports have described the karyotype and dismall clinical course (Supplementray Table S1). We performed sequential sample genomic profiling of an AML that developed in a 17-year-old female with A-T, to identify secondary genetic events towards myeloid malignancy (full clinical case history in Supplementary Information).
Humans, Ataxia Telangiectasia, Chromosome Aberrations, DNA Helicases, RNA Helicases, Gene Expression Profiling, Polymorphism, Single Nucleotide, Adolescent, Female, Tumor Suppressor Protein p53, Proto-Oncogene Proteins p21(ras), Interleukin-7 Receptor alpha Subunit, Leukemia, Myeloid, Acute, Transcriptome, Ataxia Telangiectasia Mutated Proteins, RNA Recognition Motif Proteins, Poly-ADP-Ribose Binding Proteins
MDT is funded by the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement n.310018. SM is supported by the CCLG and Bloodwise.
European Research Council (310018)
External DOI: https://doi.org/10.1002/pbc.28354
This record's URL: https://www.repository.cam.ac.uk/handle/1810/304048
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