Supplementary Figure 1. Outline of the MRC UKALL 2003 trial protocol detailing drugs used and timing schedules for the three regimens. Patients were allocated.

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Supplementary Figure 1. Outline of the MRC UKALL 2003 trial protocol detailing drugs used and timing schedules for the three regimens. Patients were allocated to therapy as detailed in the main text. Regimen Induction Consolidation Maintenance A B C Vincristine Dexamethasone Asparaginase 6-Mercaptopurine Dexamethasone 6-Mercaptopurine Dexamethasone Weeks 1-5Weeks 6-38Weeks girls boys Vincristine Dexamethasone Asparaginase Daunorubicin 6-Mercaptopurine Dexamethasone 6-Mercaptopurine Dexamethasone Weeks 1-5Weeks 6-40Weeks girls boys Vincristine Dexamethasone Asparaginase Daunorubicin 6-Mercaptopurine PEG asparaginase Methotrexate 6-Mercaptopurine Dexamethasone Weeks 1-5Weeks 6-46Weeks girls boys

r 2 = Supplementary Figure 2. Comparison of mutant levels for individual PTEN exon 7 mutants quantified in genomic DNA and whole-genome amplified (WGA) DNA. Mutant level in genomic DNA (%) Mutant level in WGA DNA (%)

Supplementary Figure 3. B-allele Frequency (BAF) and LogR ratio plots for wild-type (WT), heterozygous and homozygous PTEN deletions. 10q Mb89.7Mb PTEN (A) WT (B) Heterozygous deletion (C) Homozygous deletion `

Supplementary Figure 4. Survival stratified according to RAS genotype. (A) Relapse- free survival, (B) Overall survival. (B) 92% 86% (A) 92% 89%

Supplementary Figure 5. Survival stratified according to the oncogenetic NOTCH1/FBXW7/RAS/PTEN classification system proposed for adults. (A) Relapse-free survival, (B) Overall survival. The low-risk group have a NOTCH1 and/or FBXW7 mutation in the absence of a RAS or PTEN mutation. All other patients are in the high-risk group. (B)(A) 94% 84% 87%