Prognostic impact of INK4A deletion in Ewing sarcoma Journal Article
| Authors: | Wei, G.; Antonescu, C. R.; de Alava, E.; Leung, D.; Huvos, A. G.; Meyers, P. A.; Healey, J. H.; Ladanyi, M. |
| Article Title: | Prognostic impact of INK4A deletion in Ewing sarcoma |
| Abstract: | 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. (C) 2000 American Cancer Society. |
| Keywords: | adolescent; adult; cancer survival; child; clinical article; controlled study; human tissue; treatment outcome; bone neoplasms; bone tumor; gene deletion; doxorubicin; antineoplastic agents; follow up; gene; reverse transcription polymerase chain reaction; etoposide; tumor markers, biological; gene frequency; cyclophosphamide; vincristine; ifosfamide; ewing sarcoma; dna; carrier proteins; bleomycin; cyclin-dependent kinase inhibitor p16; sarcoma, ewing's; cdkn2a; p16; translocation; southern blotting; humans; prognosis; human; male; female; priority journal; article; dna probe; cell cycle regulator |
| Journal Title: | Cancer |
| Volume: | 89 |
| Issue: | 4 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2000-08-15 |
| Start Page: | 793 |
| End Page: | 799 |
| Language: | English |
| DOI: | 10.1002/1097-0142(20000815)89:4<793::aid-cncr11>3.0.co;2-m |
| PUBMED: | 10951342 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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