There Is No Evidence That the SDHB Gene Is Involved in Neuroblastoma Development

Abstract

Neuroblastoma and pheochromocytoma have the same embryonal origin. They originate from neural crest cells, and they usually affect suprarenal glands. The SDHB gene encodes the B subunit of succinate dehydrogenase, a protein implicated in the electron transport chain and Krebs cycle. Some mutations have been described in this gene in pheochromocytoma, and this gene could be an appropriate candidate for its study in neuroblastoma given its localization in 1p35-36. The aim of this study was to analyze neuroblastoma tumors in order to assess a possible implication of this gene in neuroblastoma development. We studied 28 neuroblastoma tumor samples from different stages. Mutation research in genomic DNA was carried out after individual amplification of each of the eight SDHB exons by SSCP analysis and sequencing of those samples with migration pattern variants. No variant was found except for three polymorphisms in four neuroblastoma samples. The first polymorphism was a synonymous A-->C change in the third position of codon 6 (exon 1). The other two polymorphisms were a TTC insert at the 5' flanking intron sequence of exon 5 in a stretch of seven TTC repeats. Upon the basis of posterior microsatellite instability and hypermethylation promoter studies, which were not significant, we can conclude that the SDHB gene, a positional candidate gene, is unlikely to be related to either initiation or tumoral progression in neuroblastoma.

Molecular characterisation of a common SDHB deletion in paraganglioma patients

“…Because neuroblastoma and PCC have the same embryological origin in the neural crest cells, usually affecting the adrenal glands, and show frequent somatic deletions affecting 1p36 where SDHB maps to, a possible role for this gene in neuroblastoma development has been suggested. Nevertheless, no SDHB point mutations have been reported in neuroblastoma patients22 23; however, no gross deletion analysis has been performed to date. Both the PGL and the neuroblastoma tumour that arose in this family showed loss of 1p36 (data not shown), as expected in these tumours 24 25.…”

Succinate dehydrogenase – Assembly, regulation and role in human disease

“…In addition, both papillary and medullary thyroid cancer have been described in patients who are SDHB or SDHD mutation carriers (Neumann, et al 2004; Zantour, et al 2004). Previously, it was thought that SDH mutations did not play a role in the development of neuroblastoma (a pediatric neuro-endocrine tumor)(Astuti, et al 2004; Grau, et al 2005). More recently, however, isolated cases of neuroblastoma have been described in 2 patients with SDHB germline deletions; one patient had an underlying family history of familial PGLs (Cascon, et al 2008) and the other patient did not (Armstrong, et al 2009).…”

MAGE-A1 expression is associated with good prognosis in neuroblastoma tumors

“…BAT-26 ampliWcation was performed using the reaction mixture and the PCR conditions described in Grau et al (2005) with primers previously described by (Alonso et al (2001). The PCR products were electrophoresed under the conditions described above.…”