Many of the most frequent actionable alterations within TMB-H tumors were within tumor suppressor pathways (PIK3CA/PTEN, CDKN2A, BRCA1/2, NF1, ATM, and TSC1/2), suggesting that many variants may be passenger rather than driver alterations in the setting of highly altered tumors. The gene discussed is CDKN2A; the disease is neoplasm.