Prognostic impact of INK4A deletion in Ewing sarcoma

Cancer. 2000 Aug 15;89(4):793-9. doi: 10.1002/1097-0142(20000815)89:4<793::aid-cncr11>;2-m.


Background: The primary genetic alteration in > 95% of Ewing sarcomas (ES) is a specific fusion of EWS with FLI1 or ERG. Secondary genetic alterations possibly involved in progression of ES are not well understood. A recent study found loss of the negative cell cycle regulator gene INK4A in 8 of 27 ES samples (30%). To confirm these findings and evaluate their prognostic significance, the authors studied INK4A deletion in 41 ES samples from 39 patients.

Methods: Using Southern blot analysis with an INK4A p16 cDNA probe, the intensity of the INK4A bands in ES DNA samples was normalized to that of a control probe and compared with nondeleted control DNA; > 50% signal reduction was scored as evidence of deletion. All ES tumor DNA samples previously were confirmed to have EWS rearrangements on the same Southern blots, using a cDNA probe spanning the EWS breakpoint region.

Results: Tumors from 7 patients (18%) showed INK4A deletion independent of disease stage (localized or metastatic) or sample source (primary tumor or metastasis). INK4A was a strong negative factor for disease specific survival in univariate analysis (P = 0.001) and in multivariate analysis including stage (relative risk = 6; P = 0.001).

Conclusions: INK4A deletions appear to be the most frequent secondary molecular genetic alteration found to date in ES. Their possible clinical usefulness in identifying a subset of ES patients with poor prognosis merits systematic prospective analysis. [See related article on pages 783-92.]

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / mortality
  • Carrier Proteins / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Gene Deletion*
  • Gene Frequency
  • Humans
  • Male
  • Prognosis
  • Sarcoma, Ewing / diagnosis
  • Sarcoma, Ewing / drug therapy
  • Sarcoma, Ewing / genetics*
  • Sarcoma, Ewing / metabolism
  • Sarcoma, Ewing / mortality
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Carrier Proteins
  • Cyclin-Dependent Kinase Inhibitor p16