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.] Copyright 2000 American Cancer Society.
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 INK4Ap16 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.] Copyright 2000 American Cancer Society.
Authors: Neerav N Shukla; Juber A Patel; Heather Magnan; Ahmet Zehir; Daoqi You; Jiabin Tang; Fanli Meng; Aliaksandra Samoila; Emily K Slotkin; Srikanth R Ambati; Alexander J Chou; Leonard H Wexler; Paul A Meyers; Ellinor I Peerschke; Agnes Viale; Michael F Berger; Marc Ladanyi Journal: JCO Precis Oncol Date: 2017-05-23
Authors: John A van Doorninck; Lingyun Ji; Betty Schaub; Hiroyuki Shimada; Michele R Wing; Mark D Krailo; Stephen L Lessnick; Neyssa Marina; Timothy J Triche; Richard Sposto; Richard B Womer; Elizabeth R Lawlor Journal: J Clin Oncol Date: 2010-03-22 Impact factor: 44.544
Authors: Daniel M Lerman; Michael J Monument; Elizabeth McIlvaine; Xiao-qiong Liu; Dali Huang; Laura Monovich; Natalie Beeler; Richard G Gorlick; Neyssa M Marina; Richard B Womer; Julia A Bridge; Mark D Krailo; R Lor Randall; Stephen L Lessnick Journal: Pediatr Blood Cancer Date: 2014-12-02 Impact factor: 3.167
Authors: R L Randall; S L Lessnick; K B Jones; L G Gouw; J E Cummings; L Cannon-Albright; J D Schiffman Journal: J Oncol Date: 2010-03-15 Impact factor: 4.375
Authors: Mona S Jahromi; Angelica R Putnam; Colleen Druzgal; Jennifer Wright; Holly Spraker-Perlman; Michelle Kinsey; Holly Zhou; Kenneth M Boucher; R Lor Randall; Kevin B Jones; David Lucas; Andrew Rosenberg; Dafydd Thomas; Stephen L Lessnick; Joshua D Schiffman Journal: Cancer Genet Date: 2012 Jul-Aug