Katia Mazzocco1, Raffaella Defferrari1, Angela Rita Sementa1, Alberto Garaventa2, Luca Longo3, Marilena De Mariano3, Maria Rosaria Esposito4, Francesca Negri1, Davide Ircolò1, Elisabetta Viscardi5, Roberto Luksch6, Paolo D'Angelo7, Arcangelo Prete8, Aurora Castellano9, Paolo Massirio2, Giovanni Erminio10, Anna Rita Gigliotti2, Gian Paolo Tonini4, Massimo Conte2. 1. Department of Pathology, Istituto Giannina Gaslini, Genova, Italy. 2. Department of Hematology-Oncology, Istituto Giannina Gaslini, Genova, Italy. 3. U.O.C. Bioterapie IRCSS A.O.U. San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. 4. Neuroblastoma Laboratory, Onco/Hematology Laboratory, SDB Department, University of Padova, Pediatric Research Institute, Fondazione Città della Speranza, Padova, Italy. 5. Department of Pediatrics, University of Padova, Padova, Italy. 6. Department of Pediatric Oncology, National Cancer Institute, Milano, Italy. 7. Department of Pediatric Hematology and Oncology, ARNAS Civico Di Cristina Benfratelli Hospital, Palermo, Italy. 8. Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", University of Bologna Sant'Orsola-Malpighi Hospital, Bologna, Italy. 9. Department of Pediatric Hematology-Oncology, IRCCS, Ospedale Bambino Gesù, Rome, Italy. 10. Department of Epidemiology and Biostatistics, Istituto Giannina Gaslini, Genova, Italy.
Abstract
BACKGROUND: Less than 5% of neuroblastomas (NB) occur in adolescents and young adults (AYA), in whom the disease has an indolent and fatal course. PROCEDURE: We studied the genomic profile and histological characteristics of 34 NBs from AYA patients enrolled in the Italian Neuroblastoma Registry (INBR) between 1979 and 2009. RESULTS: Disease was disseminated in 20 patients and localized in 14; 30/34 tumors were classified as NB and 4/34 as nodular ganglioneuroblastoma (nGNB). Segmental Chromosome Aberrations (SCAs) were observed in 29 tumors (85%) namely 1p imbalance (58%), 17q gain (52%), 9p loss (32%), 11q loss (30%), 1q gain (17%), 7q gain (17%), 2p gain (14%), 3p loss (14%), and 4p loss (7%). MYCN amplification and MYCN gain were detected in 3 (10%) and 2 cases (7%) respectively. An anaplastic lymphoma receptor tyrosine kinase (ALK) gene mutation study on the available cases from this cohort revealed 4/25 (16%) mutated cases. In parallel, alpha thalassaemia/mental retardation syndrome X linked (ATRX) gene mutations were also sought, a novel mutation being detected in 1/21 (4,7%) cases. CONCLUSION: This study confirmed the low incidence of MYCN amplification in AYA and recorded a high frequency of 17q gain and 9p and 11q loss independently from the stage of the disease. The presence of 1q gain, which identifies patients with particularly aggressive disease, relapse and poor survival, was also detected. Furthermore, the frequency of ALK mutations suggests that a target-based therapy with ALK inhibitors might be effective in this subset of patients.
BACKGROUND: Less than 5% of neuroblastomas (NB) occur in adolescents and young adults (AYA), in whom the disease has an indolent and fatal course. PROCEDURE: We studied the genomic profile and histological characteristics of 34 NBs from AYA patients enrolled in the Italian Neuroblastoma Registry (INBR) between 1979 and 2009. RESULTS: Disease was disseminated in 20 patients and localized in 14; 30/34 tumors were classified as NB and 4/34 as nodular ganglioneuroblastoma (nGNB). Segmental Chromosome Aberrations (SCAs) were observed in 29 tumors (85%) namely 1p imbalance (58%), 17q gain (52%), 9p loss (32%), 11q loss (30%), 1q gain (17%), 7q gain (17%), 2p gain (14%), 3p loss (14%), and 4p loss (7%). MYCN amplification and MYCN gain were detected in 3 (10%) and 2 cases (7%) respectively. An anaplastic lymphoma receptor tyrosine kinase (ALK) gene mutation study on the available cases from this cohort revealed 4/25 (16%) mutated cases. In parallel, alpha thalassaemia/mental retardation syndrome X linked (ATRX) gene mutations were also sought, a novel mutation being detected in 1/21 (4,7%) cases. CONCLUSION: This study confirmed the low incidence of MYCN amplification in AYA and recorded a high frequency of 17q gain and 9p and 11q loss independently from the stage of the disease. The presence of 1q gain, which identifies patients with particularly aggressive disease, relapse and poor survival, was also detected. Furthermore, the frequency of ALK mutations suggests that a target-based therapy with ALK inhibitors might be effective in this subset of patients.
Authors: Maya Suzuki; Brian H Kushner; Kim Kramer; Ellen M Basu; Stephen S Roberts; William J Hammond; Michael P LaQuaglia; Suzanne L Wolden; Nai-Kong V Cheung; Shakeel Modak Journal: Int J Cancer Date: 2018-04-06 Impact factor: 7.396
Authors: Michael R van Gerven; Eva Bozsaky; Yvette A H Matser; Julian Vosseberg; Sabine Taschner-Mandl; Jan Koster; Godelieve A M Tytgat; Jan J Molenaar; Marlinde van den Boogaard Journal: Cancer Sci Date: 2022-04-26 Impact factor: 6.518
Authors: Vid Mlakar; Simona Jurkovic Mlakar; Gonzalo Lopez; John M Maris; Marc Ansari; Fabienne Gumy-Pause Journal: Mol Cancer Date: 2017-06-29 Impact factor: 27.401