Chromosome Tumor samplesNormal samples Supplemental Figure 1.

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Supplemental Figure 1 A No. at risk T T T
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Chromosome Tumor samplesNormal samples Supplemental Figure 1

Number of protein altering mutations Number of mutations* SNV198 Indel11 Total209 Samples A Supplemental Figure 2 G>T,C>A G>C,C>G G>A,C>T A>T,T>A A>G,T>C A>C,T>G Percent B

p85 binding domain Ras binding domain C2 domain Helical domain Kinase domain E545KN202Y T313R PIK3CA Supplemental Figure 3 Phos- phatase domain C2 domain PTEN S287* V317- **Y155H

SCLC 042 SCLC 024 SCLC 018 SCLC 058 Rev. SCLC 038 PIK3CA COSMICid: 764 (Vf*: 60.7%) genome_mut_syntax: g.3: G>A aa_mut_syntax: p.E545K (Substitution-Missense) Supplemental Figure 4 PIK3CA (Vf*: 46.7%) genome_mut_syntax: g.3: A>T aa_mut_syntax: p.N202Y (Substitution-Missense) ROS1 (Vf*: 11.5%) genome_mut_syntax: g.6: C>A aa_mut_syntax: p.R2118I (Substitution-Missense) ROS1 (Vf*: 41.2%) genome_mut_syntax: g.6: C>T aa_mut_syntax: p.V1965A (Substitution-Missense) KIT (Vf*: 60.0%) genome_mut_syntax: g.4: _3 ACG del aa_mut_syntax: p.Y418del (Deletion-In frame)

AB GISTIC q score Chromosome Supplemental Figure 5

Supplemental Figure 6 copy number loss nonsense mutation frame-shift indel in-frame indel missense mutation copy number gain

A C B Supplemental Figure 7

siNC #1 #2 #3 p-AKT AKT GAPDH p-S6RP S6RP PIK3CA siPIK3CA ABC Supplemental Figure 8