PURPOSE: Neuroblastoma is characterized by two distinct types of genetic profiles, consisting of either numerical or segmental chromosome alterations. The latter are associated with a higher risk of relapse, even when occurring together with numerical alterations. We explored the role of segmental alterations in tumor progression and the possibility of evolution from indolent to aggressive genomic types. PATIENTS AND METHODS: Array-based comparative genomic hybridization data of 394 neuroblastoma samples were analyzed and linked to clinical data. RESULTS: Integration of ploidy and genomic data indicated that pseudotriploid tumors with mixed numerical and segmental profiles may be derived from pseudotriploid tumors with numerical alterations only. This was confirmed by the analysis of paired samples, at diagnosis and at relapse, as in tumors with a purely numerical profile at diagnosis additional segmental alterations at relapse were frequently observed. New segmental alterations at relapse were also seen in patients with segmental alterations at diagnosis. This was not linked to secondary effects of cytotoxic treatments since it occurred even in patients treated with surgery alone. A higher number of chromosome breakpoints were correlated with advanced age at diagnosis, advanced stage of disease, with a higher risk of relapse, and a poorer outcome. CONCLUSION: These data provide further evidence of the role of segmental alterations, suggesting that tumor progression is linked to the accumulation of segmental alterations in neuroblastoma. This possibility of genomic evolution should be taken into account in treatment strategies of low- and intermediate-risk neuroblastoma and should warrant biologic reinvestigation at the time of relapse.
PURPOSE:Neuroblastoma is characterized by two distinct types of genetic profiles, consisting of either numerical or segmental chromosome alterations. The latter are associated with a higher risk of relapse, even when occurring together with numerical alterations. We explored the role of segmental alterations in tumor progression and the possibility of evolution from indolent to aggressive genomic types. PATIENTS AND METHODS: Array-based comparative genomic hybridization data of 394 neuroblastoma samples were analyzed and linked to clinical data. RESULTS: Integration of ploidy and genomic data indicated that pseudotriploid tumors with mixed numerical and segmental profiles may be derived from pseudotriploid tumors with numerical alterations only. This was confirmed by the analysis of paired samples, at diagnosis and at relapse, as in tumors with a purely numerical profile at diagnosis additional segmental alterations at relapse were frequently observed. New segmental alterations at relapse were also seen in patients with segmental alterations at diagnosis. This was not linked to secondary effects of cytotoxic treatments since it occurred even in patients treated with surgery alone. A higher number of chromosome breakpoints were correlated with advanced age at diagnosis, advanced stage of disease, with a higher risk of relapse, and a poorer outcome. CONCLUSION: These data provide further evidence of the role of segmental alterations, suggesting that tumor progression is linked to the accumulation of segmental alterations in neuroblastoma. This possibility of genomic evolution should be taken into account in treatment strategies of low- and intermediate-risk neuroblastoma and should warrant biologic reinvestigation at the time of relapse.
Authors: Navin Pinto; Jodi R Mayfield; Gordana Raca; Mark A Applebaum; Alexandre Chlenski; Madina Sukhanova; Rochelle Bagatell; Meredith S Irwin; Anthony Little; Jawhar Rawwas; Yasmin Gosiengfiao; Olivier Delattre; Isabelle Janoueix-Lerosey; Eve Lapouble; Gudrun Schleiermacher; Susan L Cohn Journal: Pediatr Blood Cancer Date: 2016-02-10 Impact factor: 3.167
Authors: Laura E Egolf; Zalman Vaksman; Gonzalo Lopez; Jo Lynne Rokita; Apexa Modi; Patricia V Basta; Hakon Hakonarson; Andrew F Olshan; Sharon J Diskin Journal: Am J Hum Genet Date: 2019-08-29 Impact factor: 11.025
Authors: Elizabeth Sokol; Ami V Desai; Mark A Applebaum; Dominique Valteau-Couanet; Julie R Park; Andrew D J Pearson; Gudrun Schleiermacher; Meredith S Irwin; Michael Hogarty; Arlene Naranjo; Samuel Volchenboum; Susan L Cohn; Wendy B London Journal: J Clin Oncol Date: 2020-04-21 Impact factor: 44.544
Authors: Thomas F Eleveld; Derek A Oldridge; Virginie Bernard; Jan Koster; Léo Colmet Daage; Sharon J Diskin; Linda Schild; Nadia Bessoltane Bentahar; Angela Bellini; Mathieu Chicard; Eve Lapouble; Valérie Combaret; Patricia Legoix-Né; Jean Michon; Trevor J Pugh; Lori S Hart; JulieAnn Rader; Edward F Attiyeh; Jun S Wei; Shile Zhang; Arlene Naranjo; Julie M Gastier-Foster; Michael D Hogarty; Shahab Asgharzadeh; Malcolm A Smith; Jaime M Guidry Auvil; Thomas B K Watkins; Danny A Zwijnenburg; Marli E Ebus; Peter van Sluis; Anne Hakkert; Esther van Wezel; C Ellen van der Schoot; Ellen M Westerhout; Johannes H Schulte; Godelieve A Tytgat; M Emmy M Dolman; Isabelle Janoueix-Lerosey; Daniela S Gerhard; Huib N Caron; Olivier Delattre; Javed Khan; Rogier Versteeg; Gudrun Schleiermacher; Jan J Molenaar; John M Maris Journal: Nat Genet Date: 2015-06-29 Impact factor: 38.330
Authors: Wayne H Liang; Sara M Federico; Wendy B London; Arlene Naranjo; Meredith S Irwin; Samuel L Volchenboum; Susan L Cohn Journal: JCO Clin Cancer Inform Date: 2020-10