Influence of 17q gain and promoter polymorphisms on mRNA expression of somatostatin receptor type 2 in neuroblastoma.
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>G and -83 A>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>G promoter polymorphism (ANOVA: p=0.03).


CONCLUSIONS
We highlighted that 17q gain and promoter polymorphisms can play a role into the regulation of sst2 expression in neuroblastomas.
Clinical Biochemistry Units, Department of Clinical Physiopathology, University of Florence, Italy. lisa.simi@dfc.unifi.it
Lisa
L
Simi
Pamela
P
Pinzani
Claudia Casini
CC
Raggi
Mario
M
Pazzagli
Claudio
C
Orlando
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009447:Neuroblastoma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2