Influence of 17q gain and promoter polymorphisms on mRNA expression of somatostatin receptor type 2 in neuroblastoma

Abstract

Background: Neuroblastoma, the most frequent solid extracranial tumor in children, is characterized by a wide spectrum of clinical behaviours. We previously reported that high expression of somatostatin receptor type-2 (sst2) mRNA is associated to increased overall and event free survival. Several genetic abnormalities are detected in neuroblastomas, frequently involving balanced and/or unbalanced gain on the long arm on chromosome 17, the same region containing sst2 gene. Methods: In this study we detected balanced and/or unbalanced 17q gain in 50 neuroblastomas. Since two polymorphisms in sst2 promoter (− 57 C N G and − 83 A N G) were previously described as responsible for an in vitro reduction of sst2 mRNA expression, promoter sequencing was also performed in the same samples. The results were compared to sst2 mRNA expression, measured by real-time RT-PCR. Results: The frequency of 17q gain (14/50 neuroblastomas) was significantly associated to sst2 mRNA over-expression (Fischer's exact test: p = 0.0012). The sst2 expression was significant higher both in balance and unbalance 17q amplifications (ANOVA: p = 0.04). Conversely, we found a reduction of sst2 mRNA in neuroblastomas with − 57 C N G promoter polymorphism (ANOVA: p = 0.03). Conclusion: We highlighted that 17q gain and promoter polymorphisms can play a role into the regulation of sst2 expression in neuroblastomas.

Hormones, hormonal agents, and neuropeptides involved in the neuroendocrine regulation of sleep in humans

“…An unbalanced gain on chromosome 17q and promoter polymorphisms have been shown to play a role in the regulation of SST2 receptor expression, increasing overall and event-free survival in pediatric patients with neuroblastoma. 43 SRIH inhibits NREMS, presumably via its effects on GHRH secretion and stimulates REMS. 4 Interestingly, SRIH's action shows an age-dependence.…”

Differential Expression of Somatostatin Receptors, P44/42 MAPK, and mTOR Activation in Medulloblastomas and Primitive Neuroectodermal Tumors

“…10 SSR2s have also been identified on PNETs and neuroblastomas. 10,11,15,16 Their presence and in vitro evidence that SSR2-positive tumor cells are partially inhibited by the SSR2 agonist octreotide suggest that targeting SSR2 may represent a new therapeutic option. 14,17 Somatostatin analogs act, in part, by activating protein tyrosine phosphatases, which deactivate/dephosphorylate key growth-stimulating pathways especially the MAPK kinase (Raf-1)-MAPK/ERK kinase (MEK-1)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) cascade and phosphoinositide 3 kinase (PI3K)-protein kinase PKB/Akt-mTOR pathway.…”

“…4 Several studies suggest that somatostatin receptors (SSRs) or octreotide-binding sites are expressed on medulloblastomas [5][6][7][8][9] or primitive neuroectodermal tumors (PNETs) [10][11][12] and might be targeted by somatostatin ligands, such as octreotide, as a novel chemotherapy. 10,[13][14][15][16] SSR2A has been found to be overexpressed in primary and recurrent medulloblastomas. 10 SSR2s have also been identified on PNETs and neuroblastomas.…”