Olfactory neuroblastoma is a peripheral primitive neuroectodermal tumor related to Ewing sarcoma.
Olfactory neuroblastoma is a peripheral primitive neuroectodermal tumor related to Ewing sarcoma.
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嗅神经母细胞瘤是一种与尤文肉瘤相关的外周原始神经外胚层肿瘤。
DOI：
10.1073/pnas.93.3.1038
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发表时间：
1996
影响因子：
11.1
通讯作者：
T. Triche
中科院分区：
文献类型：
--
作者：
Poul H. B. Sorensen;J. K. Wu;K. Berean;J. F. Lim;W. Donn;H. Frierson;C. Reynolds;Dolores Lopez;T. Triche
嗅神经母细胞瘤是一种发生于鼻粘膜的恶性肿瘤，其组织发生机制尚不清楚。与神经母细胞瘤（NB）（一种小儿交感神经系统肿瘤）的关系是基于形态学相似性和相似神经抗原的表达。然而，ONB的临床表现不同于NB，并且未观察到NB的MYCN扩增特征。因此，我们研究了这种恶性肿瘤与其他类型的神经肿瘤的关系。在以前的研究中，两个ONB细胞系表现出细胞遗传学特征和原癌基因表达模式，提示与尤文肉瘤家族的儿童外周原始神经外胚层肿瘤（pPNTR）有关。pPN检验表明t（11; 22）（q24; q12）或t（21; 22）（q22; q12）染色体易位，将来自22 q12的EWS基因与11 q24上的FL 11基因或21 q22上的ERG基因融合。因此，我们分析了ONB中是否存在pPNET相关基因融合。两种细胞系均显示EWS基因重排，荧光原位杂交（FISH）显示EWS和FL 11基因组序列融合。此外，两个细胞系均表达EWS/FL 11融合转录物，其在EWS的外显子7和FL 11的外显子6之间具有符合读框的连接，如对pPN 11所述。我们在6例原发性ONB病例中的4例中发现了相似的基因融合。没有一个病例表达酪氨酸羟化酶，一种广泛表达于NB的儿茶酚胺生物合成酶。我们的研究表明ONB不是NB，而是pPNET家族的一员。
Olfactory neuroblastoma (ONB) is a malignant tumor of the nasal mucosa whose histogenesis is unclear. A relationship to neuroblastoma (NB), a pediatric tumor of the sympathetic nervous system, is based on morphologic similarities and the expression of similar neural antigens. However, the clinical presentation of ONB differs from that of NB, and MYCN amplification characteristic of NB is not observed. We have therefore examined the relationship of this malignancy to other classes of neural tumors. In previous studies, two ONB cell lines demonstrated cytogenetic features and patterns of protooncogene expression suggestive of a relationship to the Ewing sarcoma family of childhood peripheral primitive neuroectodermal tumors (pPNETs). The pPNETs show t(11;22)(q24;q12) or t(21;22)(q22;q12) chromosomal translocations fusing the EWS gene from 22q12 with either the FL11 gene on 11q24 or the ERG gene on 21q22. We therefore analyzed ONBs for the presence of pPNET-associated gene fusions. Both cell lines showed rearrangement of the EWS gene, and fluorescence in situ hybridization (FISH) of each case demonstrated fusion of EWS and FL11 genomic sequences. Moreover, both lines expressed EWS/FL11 fusion transcripts with in-frame junctions between exon 7 of EWS and exon 6 of FL11 as described for pPNETs. We identified similar gene fusions in four of six primary ONB cases. None of the cases expressed tyrosine hydroxylase, a catecholamine biosynthetic enzyme widely expressed in NB. Our studies indicate that ONB is not a NB but is a member of the pPNET family.