The genetic basis 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.…

• AL
  Alex's Lemonade Stand Foundation for Childhood Cancer
• WU
  Washington University in St. Louis
• AL
  American Lebanese Syrian Associated Charities

  Award: CA021765
• AJ
  Alvin J. Siteman Cancer Center
• CO
  Children’s Oncology Group
• NI
  National Institutes of Health

  Awards: U54 HG003079, CA021765, P30 CA021765, HG003079, CA98413, CA114766, CA98543
• NH
  National Human Genome Research Institute

  Awards: U54 HG003079, HG003079, NHGRI U54 HG003079
• NC
  National Cancer Institute

  Awards: CA114766, CA98543, CA021765, P30 CA021765, CA98413, U54 HG003079