Frequent promoter hypermethylation of the APC and RASSF1A tumour suppressors in parathyroid tumours
| Autor: | C. Christofer Juhlin, Andrea Villablanca, Catharina Larsson, Nimrod B Kiss, Jörgen Nordenström, Anders Höög, Felix Haglund |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adenoma
medicine.medical_specialty Genes APC Genotype Receptors Retinoic Acid Science Adenomatous Polyposis Coli Protein Biology medicine.disease_cause Epigenesis Genetic Parathyroid Glands Internal medicine Genetics and Genomics/Epigenetics medicine Humans MEN1 Epigenetics Diabetes and Endocrinology/Multiple Endocrine Disorders and Neoplasias Promoter Regions Genetic Genetics and Genomics/Cancer Genetics Cyclin-Dependent Kinase Inhibitor p16 Genetics and Genomics/Genetics of Disease Multidisciplinary Gene Expression Profiling Tumor Suppressor Proteins Methylation DNA Methylation medicine.disease Gene Expression Regulation Neoplastic Endocrinology Long Interspersed Nucleotide Elements Parathyroid Neoplasms DNA methylation Cancer research Medicine CpG Islands Sample collection Carcinogenesis Primary hyperparathyroidism Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 3, p e9472 (2010) |
| ISSN: | 1932-6203 |
| Popis: | BackgroundParathyroid adenomas constitute the most common entity in primary hyperparathyroidism, and although recent advances have been made regarding the underlying genetic cause of these lesions, very little data on epigenetic alterations in this tumour type exists. In this study, we have determined the levels of promoter methylation regarding the four tumour suppressor genes APC, RASSF1A, p16(INK4A) and RAR-beta in parathyroid adenomas. In addition, the levels of global methylation were assessed by analyzing LINE-1 repeats.Methodology/principal findingsThe sample collection consisted of 55 parathyroid tumours with known HRPT2 and/or MEN1 genotypes. Using Pyrosequencing analysis, we demonstrate APC promoter 1A and RASSF1A promoter hypermethylation in the majority of parathyroid tumours (71% and 98%, respectively). Using TaqMan qRT-PCR, all tumours analyzed displayed lower RASSF1A mRNA expression and higher levels of total APC mRNA than normal parathyroid, the latter of which was largely conferred by augmented APC 1B transcription levels. Hypermethylation of p16(INK4A) was demonstrated in a single adenoma, whereas RAR-beta hypermethylation was not observed in any sample. Moreover, based on LINE-1 analyses, parathyroid tumours exhibited global methylation levels within the range of non-neoplastic parathyroid tissues.Conclusions/significanceThe results demonstrate that APC and RASSF1A promoter hypermethylation are common events in parathyroid tumours. While RASSF1A mRNA levels were found downregulated in all tumours investigated, APC gene expression was retained through APC 1B mRNA levels. These findings suggest the involvement of the Ras signaling pathway in parathyroid tumorigenesis. Additionally, in contrast to most other human cancers, parathyroid tumours were not characterized by global hypomethylation, as parathyroid tumours exhibited LINE-1 methylation levels similar to that of normal parathyroid tissues. |
| Databáze: | OpenAIRE |
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