1. Genomic profiling of acute myeloid leukaemia associated with ataxia telangiectasia identifies a complex karyotype with wild-type TP53 and mutant KRAS, G3BP1 and IL7R
- Author
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Goldgraben, Mae A, Fewings, Eleanor, Larionov, Alexey, Scarth, James, Redman, James, Telford, Nick, Arkwright, Peter D, Bonney, Denise, Wilks, Deepti, Kulkarni, Samar, Taylor, A Malcolm R, Tischkowitz, Marc D, Meyer, Stefan, Goldgraben, Mae A [0000-0002-1111-2804], Meyer, Stefan [0000-0002-2283-3690], and Apollo - University of Cambridge Repository
- Subjects
Chromosome Aberrations ,Adolescent ,Gene Expression Profiling ,DNA Helicases ,Ataxia Telangiectasia Mutated Proteins ,Polymorphism, Single Nucleotide ,Interleukin-7 Receptor alpha Subunit ,Proto-Oncogene Proteins p21(ras) ,Ataxia Telangiectasia ,Leukemia, Myeloid, Acute ,RNA Recognition Motif Proteins ,Humans ,Female ,Tumor Suppressor Protein p53 ,Poly-ADP-Ribose Binding Proteins ,Transcriptome ,RNA Helicases - Abstract
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).
- Published
- 2020