Genetic abnormalities in adolescents and young adults with neuroblastoma: A report from the Italian Neuroblastoma group.
BACKGROUND
Less than 5% of neuroblastomas (NB) occur in adolescents and young adults (AYA), in whom the disease has an indolent and fatal course.


METHODS
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.


CONCLUSIONS
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.
Department of Pathology, Istituto Giannina Gaslini, Genova, Italy.
Katia
K
Mazzocco
Department of Pathology, Istituto Giannina Gaslini, Genova, Italy.
Raffaella
R
Defferrari
Department of Pathology, Istituto Giannina Gaslini, Genova, Italy.
Angela Rita
AR
Sementa
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genova, Italy.
Alberto
A
Garaventa
U.O.C. Bioterapie IRCSS A.O.U. San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Luca
L
Longo
U.O.C. Bioterapie IRCSS A.O.U. San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Marilena
M
De Mariano
Neuroblastoma Laboratory, Onco/Hematology Laboratory, SDB Department, University of Padova, Pediatric Research Institute, Fondazione Città della Speranza, Padova, Italy.
Maria Rosaria
MR
Esposito
Department of Pathology, Istituto Giannina Gaslini, Genova, Italy.
Francesca
F
Negri
Department of Pathology, Istituto Giannina Gaslini, Genova, Italy.
Davide
D
Ircolò
Department of Pediatrics, University of Padova, Padova, Italy.
Elisabetta
E
Viscardi
Department of Pediatric Oncology, National Cancer Institute, Milano, Italy.
Roberto
R
Luksch
Department of Pediatric Hematology and Oncology, ARNAS Civico Di Cristina Benfratelli Hospital, Palermo, Italy.
Paolo
P
D'Angelo
Pediatric Oncology and Hematology Unit "Lalla Seràgnoli", University of Bologna Sant'Orsola-Malpighi Hospital, Bologna, Italy.
Arcangelo
A
Prete
Department of Pediatric Hematology-Oncology, IRCCS, Ospedale Bambino Gesù, Rome, Italy.
Aurora
A
Castellano
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genova, Italy.
Paolo
P
Massirio
Department of Epidemiology and Biostatistics, Istituto Giannina Gaslini, Genova, Italy.
Giovanni
G
Erminio
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genova, Italy.
Anna Rita
AR
Gigliotti
Neuroblastoma Laboratory, Onco/Hematology Laboratory, SDB Department, University of Padova, Pediatric Research Institute, Fondazione Città della Speranza, Padova, Italy.
Gian Paolo
GP
Tonini
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genova, Italy.
Massimo
M
Conte
D000293:Adolescent; D000328:Adult; D002648:Child; D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007558:Italy; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
ATRX; adolescents; genetics; neuroblastoma