Amplified genes negatively associated IS scores include well-known driver oncogenes such as MYC and E2F3 while deleted genes with negative association include well-known tumor suppressor genes such as RB1, TP53, and PTEN. Importantly, recent study demonstrated that loss of PTEN is indeed significantly associated with resistant to immunotherapy with anti-PD-1 antibodies in melanoma54, strongly suggesting that many of identified candidates might play key roles in host immunity to cancer cells. The gene discussed is RB1; the disease is cancer.