BACKGROUND. The primary genetic alteration, in > 95% of Ewing sarcomas (ES) is involoed in progression of ES are not well understood. A recent study found loss of the negative cell cyde rcgulator gene INK4A in 8 at 27 FS samples (13%) To confirm these findings and cvaluate their prognostic Significanoe, Lhe authors studied INK4A deletion in 41 ES samples from 39 patiens. METHODS Using Soulthem blot analysis with an INK4A p16 cDNA probe, the control probe and compared with nondeleted eonrol DNA; > 50% signal reduction was scored as evidence of deletion All NS tumor DNA samples previously were confirmed to have EWS rearrangremetnts on the same Soulhum blots, Using a cDNA probe spanning the EWS breakpoint region. RESULTS. Tumors from 7 Datients (18%) showed INK4A deletion indenendent of tasis INK4A was. strong negative facror for disease specific surviat in Univafate CONCLUSIONS. INK4A deletions appear to be the most frequent seeondary molec-ular genetic alteration faund la date in ES. Their possible clinical usefulness in identifying a subset or ES patents with poor prognosis merits systematic prospec tive analysts See related article on pages 783-92.