Mazzocco Katia, Defferrari Raffaella, Sementa Angela Rita, Garaventa Alberto, Longo Luca, De Mariano Marilena, Esposito Maria Rosaria, Negri Francesca, Ircolò Davide, Viscardi Elisabetta, Luksch Roberto, D'Angelo Paolo, Prete Arcangelo, Castellano Aurora, Massirio Paolo, Erminio Giovanni, Gigliotti Anna Rita, Tonini Gian Paolo, Conte Massimo
Department of Pathology, Istituto Giannina Gaslini, Genova, Italy.
Department of Hematology-Oncology, Istituto Giannina Gaslini, Genova, Italy.
Pediatr Blood Cancer. 2015 Oct;62(10):1725-32. doi: 10.1002/pbc.25552. Epub 2015 Apr 29.
Less than 5% of neuroblastomas (NB) occur in adolescents and young adults (AYA), in whom the disease has an indolent and fatal course.
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.
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.
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.
不到5%的神经母细胞瘤（NB）发生于青少年和青年（AYA），这类患者的疾病进程呈惰性但致命。
我们研究了1979年至2009年间纳入意大利神经母细胞瘤登记处（INBR）的AYA患者的34例NB的基因组特征和组织学特征。
20例患者疾病已播散，14例局限；34例肿瘤中30例分类为NB，4例为结节性神经节神经母细胞瘤（nGNB）。29例肿瘤（85%）观察到节段性染色体畸变（SCA），即1p失衡（58%）、17q增益（52%）、9p缺失（32%）、11q缺失（30%）、1q增益（17%）、7q增益（17%）、2p增益（14%）、3p缺失（14%）和4p缺失（7%）。分别在3例（10%）和2例（7%）中检测到MYCN扩增和MYCN增益。对该队列中可用病例进行的间变性淋巴瘤受体酪氨酸激酶（ALK）基因突变研究显示4/25（16%）例发生突变。同时，还寻找了X连锁的α地中海贫血/智力发育迟缓综合征（ATRX）基因突变，在1/21（4.7%）例中检测到一种新突变。
本研究证实AYA中MYCN扩增发生率低，并记录了17q增益以及9p和11q缺失的高频率，且与疾病分期无关。还检测到1q增益的存在，其可识别疾病侵袭性特别强、复发且生存不良的患者。此外，ALK突变的频率表明，用ALK抑制剂进行基于靶点的治疗可能对这部分患者有效。
