In ES, genetic alterations affecting the pRB-dependent cell-cycle regulation pathway have been described including deletions of both CDKN2A (INK4A/ARF) and RB1. Kovar et al. (1997) first described CDKN2A deletions in 30% of tumors (N = 8/27) and 52% of ES cell lines (N = 12/23) and several retrospective studies have demonstrated an association between CDKN2A alterations and clinical outcome in ES patients. The gene discussed is RB1; the disease is Ewing sarcoma.