Abstract：
BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumour in childhood with a diverse clinical presentation and course. The early age of onset, high frequency of metastatic disease at diagnosis and tendency for spontaneous regression in infancy sets it apart from other childhood tumors. This heterogeneity is largely attributed to underlying genetic aberrations which are distinct in low-risk and high-risk NB. To this end, we sought to analyse our NB cases for the molecular alterations and find its correlation with clinical behaviour.
METHODS: NB cases (n = 50) diagnosed over last 7 years were retrospectively analysed for MYCN amplification (fluorescent-in-situ hybridization), TERT rearrangements (qRT-PCR), ATRX mutations (immunohistochemistry). These findings were correlated with demographic profiles, histologic features and clinical outcome.
RESULTS: Age ranged from 1 month to 30 years (mean 2.8 years) with male preponderance. Poorly differentiated subtype constituted the majority (64%), followed by differentiating (28%) and undifferentiated subtype (8%) which were equally distributed across all age groups. MYCN amplification, TERT-mRNA upregulation and ATRX mutations was observed in 30%, 42% and 24%, respectively. Cases with TERT-mRNA upregulation were distributed equally across all histological subtypes while those with ATRX mutations and MYCN amplification were frequent in poorly differentiated NB. ATRX mutation was mutually exclusive of TERT-mRNA upregulation and MYCN amplification. Kaplan-Meier analysis revealed significantly shorter overall and progression-free survival for tumors harboring MYCN amplification and TERT-mRNA upregulation, while that for ATRX mutant tumors was not significant.
CONCLUSIONS: Our results provide data indicating poor clinical outcome in NB carrying MYCN amplification and TERT-mRNA upregulation.
METHODS: NB cases (n = 50) diagnosed over last 7 years were retrospectively analysed for MYCN amplification (fluorescent-in-situ hybridization), TERT rearrangements (qRT-PCR), ATRX mutations (immunohistochemistry). These findings were correlated with demographic profiles, histologic features and clinical outcome.
RESULTS: Age ranged from 1 month to 30 years (mean 2.8 years) with male preponderance. Poorly differentiated subtype constituted the majority (64%), followed by differentiating (28%) and undifferentiated subtype (8%) which were equally distributed across all age groups. MYCN amplification, TERT-mRNA upregulation and ATRX mutations was observed in 30%, 42% and 24%, respectively. Cases with TERT-mRNA upregulation were distributed equally across all histological subtypes while those with ATRX mutations and MYCN amplification were frequent in poorly differentiated NB. ATRX mutation was mutually exclusive of TERT-mRNA upregulation and MYCN amplification. Kaplan-Meier analysis revealed significantly shorter overall and progression-free survival for tumors harboring MYCN amplification and TERT-mRNA upregulation, while that for ATRX mutant tumors was not significant.
CONCLUSIONS: Our results provide data indicating poor clinical outcome in NB carrying MYCN amplification and TERT-mRNA upregulation.
摘要：
背景：神经母细胞瘤（NB）是儿童时期最常见的颅外实体瘤，临床表现和病程多样。发病年龄较早，在诊断时转移性疾病的频率很高，并且在婴儿期自发消退的趋势使其与其他儿童肿瘤不同。这种异质性在很大程度上归因于潜在的遗传畸变，这在低风险和高风险NB中是不同的。为此,我们试图分析NB病例的分子改变,并发现其与临床行为的相关性.
方法：过去7年确诊的NB病例（n=50）回顾性分析MYCN扩增（荧光原位杂交），TERT重排（qRT-PCR），ATRX突变（免疫组织化学）。这些发现与人口统计学特征相关，组织学特征和临床结果。
结果：年龄1个月至30岁（平均2.8岁），男性占优势。低分化亚型占大多数（64％），其次是分化（28％）和未分化亚型（8％），它们在所有年龄组中分布均匀。MYCN扩增,在30%中观察到TERT-mRNA上调和ATRX突变,42%和24%，分别。TERT-mRNA上调的病例在所有组织学亚型中分布均匀，而ATRX突变和MYCN扩增的病例在低分化NB中频繁发生。ATRX突变与TERT-mRNA上调和MYCN扩增互斥。Kaplan-Meier分析显示，MYCN扩增和TERT-mRNA上调的肿瘤的总生存期和无进展生存期显著缩短，而对于ATRX突变肿瘤则不显著。
结论：我们的结果提供的数据表明，携带MYCN扩增和TERT-mRNA上调的NB的临床结局较差。
方法：过去7年确诊的NB病例（n=50）回顾性分析MYCN扩增（荧光原位杂交），TERT重排（qRT-PCR），ATRX突变（免疫组织化学）。这些发现与人口统计学特征相关，组织学特征和临床结果。
结果：年龄1个月至30岁（平均2.8岁），男性占优势。低分化亚型占大多数（64％），其次是分化（28％）和未分化亚型（8％），它们在所有年龄组中分布均匀。MYCN扩增,在30%中观察到TERT-mRNA上调和ATRX突变,42%和24%，分别。TERT-mRNA上调的病例在所有组织学亚型中分布均匀，而ATRX突变和MYCN扩增的病例在低分化NB中频繁发生。ATRX突变与TERT-mRNA上调和MYCN扩增互斥。Kaplan-Meier分析显示，MYCN扩增和TERT-mRNA上调的肿瘤的总生存期和无进展生存期显著缩短，而对于ATRX突变肿瘤则不显著。
结论：我们的结果提供的数据表明，携带MYCN扩增和TERT-mRNA上调的NB的临床结局较差。
