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  • Title: Deletions and altered expression of the RIZ1 tumour suppressor gene in 1p36 in pheochromocytomas and abdominal paragangliomas.
    Author: Geli J, Nord B, Frisk T, Edström Elder E, Ekström TJ, Carling T, Bäckdahl M, Larsson C.
    Journal: Int J Oncol; 2005 May; 26(5):1385-91. PubMed ID: 15809732.
    Abstract:
    Pheochromocytomas and abdominal paragangliomas are rare catecholamine-producing tumours arising from neural crest-derived chromaffin cells. Frequent deletions of several distinct regions on the short arm of chromosome 1 suggest their involvement in the tumourigenesis process. The RIZ1 tumour suppressor encoded by the RIZ gene in 1p36.21 represents an attractive candidate target for the distal 1p deletions in these tumours. A panel of 18 pheochromocytomas (14 benign, and 4 malignant) and 11 abdominal paragangliomas (4 benign, and 7 malignant) were characterised for somatic deletions and mRNA expression status of RIZ1 using loss of heterozygosity (LOH) analysis and real-time quantitative PCR, respectively. Furthermore, we evaluated the methylation status of the RIZ1 promoter utilising methylation-specific PCR (MSP). Intragenic LOH at the RIZ locus was detected in 10 of 16 informative cases (62%), including 8 of 12 pheochromocytomas (67%) and 2 of 4 paragangliomas (50%). RIZ1 mRNA appeared to be significantly under-expressed in the tumour samples compared to normal adrenal controls (mean 0.6 vs. 1.0, p<0.001). This was not associated with RIZ1 promoter methylation in any of the samples, indicating that promoter hypermethylation is unlikely to be the underlying cause of the frequent expressional silencing. The recurrent inactivation of the tumour suppressor RIZ1 suggests that this event may be a significant contributing factor to tumour development in pheochromocytomas and abdominal paragangliomas.
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