The genetic basis of early T-cell precursor acute lymphoblastic leukaemia

By Jinghui Zhang, L. Ding, L. Holmfeldt, Gang Wu, S. Heatley, D. Payne-Turner, J. Easton, Xiang Chen, Jianmin Wang, M. Rusch and 59 more. Nature, 2012

1,571 citations recorded by the source corpus.

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.

Subfields: Hematology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/eb2898ee3f2bdf40652ae14f2aeebc999743ada8

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In Hematology

1. M. Dawson
2. Tony Kouzarides
3. Richard A. Young
4. Denes Hnisz

In Public Health, Environmental and Occupational Health

1. Ching-Hon Pui
2. R. Jaenisch

Citations in the corpus

• Signatures of mutational processes in human cancer (2013, neutral): “However,inSupplementaryInformationwealsoprovideavisualizationofmuta-tionalsignaturesbasedonanequalfrequencyofeachtrinucleotide(Supplemen-taryFigs2–28).”
• Cancer epigenetics: from mechanism to therapy. (2012, background): “, 2010) and T-ALL (Ntziachristos et al., 2012; Zhang et al., 2012), suggesting a tumor-suppressive role for EZH2 in these cell lineages.”
• Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia (2012, methodology): “We used multiple complementary analysis pipelines, including deFuse (McPherson et al., 2011), Mosaik (Marth, 2010), CREST (Wang et al., 2011), CONSERTING (Zhang et al., 2012), and Trans-ABySS (Robertson et al., 2010) to identify rearrangements, structural variations, and sequence mutations.”