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The genetic basis of early T-cell precursor acute lymphoblastic leukaemia
- Source :
- Nature. 481:157-163
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.
- Subjects :
- Neuroblastoma RAS viral oncogene homolog
Myeloid
DNA Copy Number Variations
T-Lymphocytes
Molecular Sequence Data
Biology
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
medicine.disease_cause
Article
Translocation, Genetic
Histones
hemic and lymphatic diseases
medicine
Humans
Genetic Predisposition to Disease
Age of Onset
Child
EP300
Interleukin-7 receptor
Janus Kinases
Receptors, Interleukin-7
Multidisciplinary
Genome, Human
Stem Cells
Genomics
Sequence Analysis, DNA
medicine.disease
Hematopoiesis
Leukemia, Myeloid, Acute
Reelin Protein
DNM2
Haematopoiesis
Leukemia
Genes, ras
medicine.anatomical_structure
Mutation
Immunology
Cancer research
KRAS
Signal Transduction
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 481
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....4269ed08f37c26096bb98c3c790bea38