There is significant allelic variation in PspA and PspC structure

In a next step, it will be interesting to determine with accuracy genes implicated in the amplicons using next generation sequencing. Interestingly, patients with NBs harbouring amplifications other than MYCN, without concomitant MNA, constitute a heterogeneous group of patients with NBs arising from non adrenal sites observed more frequently, as well as occurrence of atypical metastatic sites. Furthermore an increased frequency of absence of MIBG avidity and absence of urinary CX-4945 catecholamine secretion was noted, when normally positive in 90�C 95% of NB cases. In addition to atypical NVP-BEZ235 clinical features, the overall genomic pattern of these NBs revealed atypical segmental patterns. Although histological analysis confirmed the diagnosis of NB, novel histology characterisation using PHOX2B immunostaining might be useful in this context of atypical NB to help in the diagnosis of undifferentiated types. Indeed PHOX2B immunolabelling has been shown to improve the diagnosis of undifferentiated NB among childhood small round blue-cell tumours with high specificity and sensitivity. Considering recent publication, it would be also interesting for this atypical group of NB without MNA to further study expression of MYC protein in the tumour as it has been suggested that MYC protein expression could be a new prognostic factor indicating more aggressive clinical behaviour than MNA. On the other hand, clinical features of patients whose tumours harbour regional amplifications other than MYCN together with MNA are comparable to those with MNA only. Although limited by the small number of patients, analysis suggests that OS of patients with amplification other than MYCN without MNA might be better than that of patients with MNA, whereas those harbouring both MYCN and other amplifications might have an even worse prognosis. Indeed tumours harbouring regional amplicons in addition to MNA showed a higher genomic instability as documented by the observation of more segmental chromosomal alterations with a tendency towards a poorer outcome, as suggested previously.

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