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Genetic landscape of Early T-cell precursor acute lymphoblastic leukaemia

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.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001052 Illumina HiSeq 2000 24
EGAD00001001352 Illumina HiSeq 2000 38
EGAD00001001432 Illumina HiSeq 2000 1337
EGAD00001001433 Illumina HiSeq 2000 906
Publications Citations
CREST maps somatic structural variation in cancer genomes with base-pair resolution.
Nat Methods 8: 2011 652-654
344
Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data.
Genome Biol 13: 2012 R113
22
Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.
PLoS Genet 11: 2015 e1005262
73
The evolution of relapse of adult T cell acute lymphoblastic leukemia.
Genome Biol 21: 2020 284
7