REGRESSION AND PROGRESSION IN NEUROBLASTOMA - DOES GENETICS PREDICT TUMOR BEHAVIOR
REGRESSION AND PROGRESSION IN NEUROBLASTOMA - DOES GENETICS PREDICT TUMOR BEHAVIOR
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DOI：
10.1016/0959-8049(95)00044-j
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发表时间：
1995-01-01
影响因子：
8.4
通讯作者：
GADNER, H
中科院分区：
文献类型：
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作者：
AMBROS, PF;AMBROS, IM;GADNER, H
神经母细胞瘤（NB）是一种异质性疾病。临床过程可能从自发的退化和成熟到非常具有攻击性的行为。状态4s是NB的一个独特亚类，通常与良好的预后相关，尽管皮肤和/或肝脏受累以及骨髓中经常存在肿瘤细胞。另一种类型的NB是没有骨和骨髓受累的局部浸润性肿瘤，其也可以具有良好的预后，而不管淋巴结受累。不幸的是，尽管淋巴结受累、手术后残留肿瘤块和/或骨髓浸润，但这些肿瘤尚未用细胞毒性疗法治疗，关于这些肿瘤的生物学信息仅有限。为了找到具有良性临床过程的NB常见的特定遗传变化，我们研究了这些肿瘤的遗传异常，并将其与高度侵袭性肿瘤进行了比较。我们分析了一系列的54个本地化和4S期肿瘤的新鲜细胞或石蜡包埋组织上进行原位杂交的手段。此外，我们对新鲜肿瘤组织进行了经典的细胞遗传学、Southern印迹和PCR分析。大多数患者仅接受手术治疗，一些患者的肿瘤切除不完全。缺失在1p36和扩增的MYCN癌基因是不存在的，二倍体或四倍体在任何情况下都没有看到，与残留的局部肿瘤拥有一个有利的结果。出乎意料的是，一名没有任何遗传结构变化的四倍体4s肿瘤患者没有接受任何细胞毒性治疗，表现良好。有趣的是，这种遗传谱与进展性肿瘤形成对比，其中大多数具有遗传畸变，1p36的缺失是最常见的事件。这些数据虽然有限，但表明完整的1p36（由D1Z2识别），MYCN扩增的缺乏和近三倍体（至少在局部肿瘤中），代表了自发消退和/或成熟的先决条件。
Neuroblastoma (NB) is a heterogeneous disease. The clinical course may range from spontaneous regression and maturation to very aggressive behaviour. State 4s is a unique subcategory of NB, generally associated with good prognosis, despite skin and/or liver involvement and the frequent presence of tumour cells in the bone marrow. Another type of NB is the locally invasive tumour without bone and bone marrow involvement which can also have a good prognosis, irrespective of lymph node involvement. Unfortunately, there is only limited biological information on such tumours which have not been treated with cytotoxic therapy despite lymph node involvement, residual tumour mass after surgery and/or bone marrow infiltration. In order to find specific genetic changes common to NBs with a benign clinical course, we studied the genetic abnormalities of these tumours and compared them with highly aggressive tumours. We analysed a series of 54 localised and stage 4s tumours by means of in situ hybridisation performed on fresh cells or on paraffin embedded tissues. In addition, we performed classical cytogenetics, Southern blotting and PCR analysis on fresh tumour tissue. The majority of patients had been treated with surgery alone, and in a number of patients tumour resection was incomplete. Deletions at 1p36 and amplifications of the MYCN oncogene were absent, and diploidy or tetraploidy were not seen in any case, with residual localised tumours possessing a favourable outcome. Unexpectedly, one patient with a tetraploid 4s tumour without any genetic structural changes not receiving any cytotoxic treatment, did well. Interestingly, this genetic spectrum contrasted with that of progressing tumours, in which most had genetic aberrations, the deletion at 1p36 being the most common event. These data, although limited, suggest that an intact 1p36 (recognised by D1Z2), the absence of MYCN amplification and near-triploidy (at least in localised tumours), represent prerequisites for spontaneous regression and/or maturation.