Supplementary Figure 1. Correlation with Number of Alterations Per Sample and Progression-Free

Supplementary Table 1A. A list of all mutations presented in Figure 1A, annotated by gene, mutation, amino acid change, type and tier.

Supplementary Table 1B. Examples of Patients Enrolled on Clinical Trial with Agents Matched or Unmatched to Genomic Alteration.

Supplementary Figure 1. Correlation with Number of Alterations per Sample and Progression-Free Survival.

Histograms show the frequency of samples binned by the number of SNV or CNV alterations. The median numbers of alterations detected across the Oncopanel cohort is 4 SNVs and 17 CNVs. Kaplan-Meier estimates of survival show no difference in progression-free survival based on high or low alterations, separated by upper quartile or lower quartile number of events.

Supplementary Figure 2. Presence of IKZF1 Amplification is Associated with Progression-Free Survival Across the Oncopanel Cohort (n=109). Kaplan-Meier estimates of survival show a difference in progression-free survival based on IKZF1 amplification status.

Supplementary Figure 3. Presence of MCL1 Amplification is Associated with Progression-Free Survival Across the Oncopanel Cohort (n=109). Kaplan-Meier estimates of survival show a difference in progression-free survival based on MCL1 amplification status.

Supplementary Figure 4. Presence of PIK3CA Amplification is Associated with Overall Survival Across the Oncopanel Cohort (n=109). Kaplan-Meier estimates of survival show a difference in overall survival based on PIK3CA amplification status.

Supplementary Figure 5. Presence of NRAS Mutations or Copy Number Gain is Associated with Overall Survival Across the Oncopanel Cohort (n=109). Kaplan-Meier estimates of survival show a difference in overall survival based on NRAS mutation or copy number gain.

Supplementary Figure 6. Presence of GATA4 Amplification is Associated with Overall Survival Across the Oncopanel Cohort (n=109). Kaplan-Meier estimates of survival show a difference in overall survival based on GATA4 amplification status.

Supplementary Figure 7. Presence of PIK3CA Tier1/2 Mutations Alone, without Considering Copy Number Amplifications, is not Associated with Progression-Free Survival Across the HNSCC Cohort (n=213). Kaplan-Meier estimates of survival show no difference in progression-free survival based on PIK3CA Tier1/2 mutation status.