Non-coding RNA <it>ANRIL</it> and the number of plexiform neurofibromas in patients with <it>NF1</it> microdeletions
<p>Abstract</p> <p>Background</p> <p>Neurofibromatosis type-1 (NF1) is caused by mutations of the <it>NF1</it> gene at 17q11.2. In 95% of non-founder NF1 patients, <it>NF1</it> mutations are identifiable by means of a comprehensive mutation analy...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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BMC,
2012-10-01T00:00:00Z.
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| Summary: | <p>Abstract</p> <p>Background</p> <p>Neurofibromatosis type-1 (NF1) is caused by mutations of the <it>NF1</it> gene at 17q11.2. In 95% of non-founder NF1 patients, <it>NF1</it> mutations are identifiable by means of a comprehensive mutation analysis. 5-10% of these patients harbour microdeletions encompassing the <it>NF1</it> gene and its flanking regions. NF1 is characterised by tumours of the peripheral nerve sheaths, the pathognomonic neurofibromas. Considerable inter- and intra-familial variation in expressivity of the disease has been observed which is influenced by genetic modifiers unrelated to the constitutional <it>NF1</it> mutation. The number of plexiform neurofibromas (PNF) in NF1 patients is a highly heritable genetic trait. Recently, SNP rs2151280 located within the non-coding RNA gene <it>ANRIL</it> at 9p21.3, was identified as being strongly associated with PNF number in a family-based association study. The T-allele of rs2151280, which correlates with reduced <it>ANRIL</it> expression, appears to be associated with higher PNF number. <it>ANRIL</it> directly binds to the SUZ12 protein, an essential component of polycomb repressive complex 2, and is required for SUZ12 occupancy of the <it>CDKN2A/CDKN2B</it> tumour suppressor genes as well as for their epigenetic silencing.</p> <p>Methods</p> <p>Here, we explored a potential association of PNF number and PNF volume with SNP rs2151280 in 29 patients with constitutional <it>NF1</it> microdeletions using the exact Cochran-Armitage test for trends and the exact Mann-Whitney-Wilcoxon test. Both the PNF number and total tumour volume in these 29 NF1 patients were assessed by whole-body MRI. The <it>NF1</it> microdeletions observed in these 29 patients encompassed the <it>NF1</it> gene as well as its flanking regions, including the <it>SUZ12</it> gene.</p> <p>Results</p> <p>In the 29 microdeletion patients investigated, neither the PNF number nor PNF volume was found to be associated with the T-allele of rs2151280.</p> <p>Conclusion</p> <p>Our findings imply that, at least in patients with <it>NF1</it> microdeletions, PNF susceptibility is not associated with rs2151280. Although somatic inactivation of the <it>NF1</it> wild-type allele is considered to be the PNF-initiating event in NF1 patients with intragenic mutations and patients with <it>NF1</it> microdeletions, both patient groups may differ with regard to tumour progression because of the heterozygous constitutional deletion of <it>SUZ12</it> present only in patients with <it>NF1</it> microdeletions.</p> |
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| Item Description: | 10.1186/1471-2350-13-98 1471-2350 |