Frequent Promoter Hypermethylation of the APC and RASSF1A Tumour Suppressors in Parathyroid Tumours

Juhlin, C. Christofer; Kiss, Nimrod; Villablanca, Andrea; Haglund, Felix; Nordenström, Jörgen; Höög, Anders; Larsson, Catharina

doi:10.1371/journal.pone.0009472

Cited by 57 publications

(58 citation statements)

References 46 publications

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“…The methylation status of promoter regions has also been analysed in parathyroid tumours (Starker et al 2011) and frequent hypermethylation of RIZ1/PRDM2, CDKN2A, RASSF1A and APC genes has been reported (Carling et al 2003, Juhlin et al 2010, Svedlund et al 2010.…”

Section: Discussionmentioning

confidence: 99%

The microRNA cluster C19MC is deregulated in parathyroid tumours

Vaira¹,

Elli²,

Forno³

et al. 2012

Journal of Molecular Endocrinology

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A subset of over-expressed microRNAs (miRNAs) identified in parathyroid carcinomas (Ca) compared to normal glands belongs to C19MC, a cluster on chromosome 19q13.4 involved in stem cell biology and tumourigenesis. In this study, the expression of C19MC-MIR371-3 clusters and the molecular mechanisms presiding their modulation were investigated in a series of six normal parathyroids, 24 adenomas (Ad), 15 Ca and five matched metastases. The general expression levels of C19MC or MIR371-3 clusters in Ad lesions did not differ from normal glands, while they distinguished Ad from Ca at unsupervised hierarchical cluster analysis (PZ0 . 0008). MIR517C showed the most significant difference in expression between Ca and Ad (PZ0 . 0003) and it positively correlated with serum calcium, parathormone and tumour weight. In regard to the molecular mechanism determining C19MC cluster activation, we could detect C19MC copy number (CN) gain in ten Ca (67%) extending distal to the MIR371-3 cluster in almost all samples. Conversely, only four Ad (16%) showed C19MC amplification, with one case presenting distal genomic aberration to MIR371-3. Globally, CN variations of 19q13.4 loci were significantly associated with MIR517C up-regulation (PZ0 . 006). Opposite to normal glands where C19MC promoter was methylated, hypomethylation occurred in 15 out of 30 analysed tumours. Though the epigenetic status did not correlate with C19MC miRNA expression levels, loss of C19MC promoter methylation was significantly associated with Ca and metastatic disease (PZ0 . 01). In conclusion, C19MC cluster aberrations are a characteristic of Ca with respect to Ad. Altogether, these evidences point towards a role for 19q13.4 miRNA clusters as oncogenes in parathyroid tumourigenesis.

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Section: Discussionmentioning

confidence: 99%

The microRNA cluster C19MC is deregulated in parathyroid tumours

Vaira¹,

Elli²,

Forno³

et al. 2012

Journal of Molecular Endocrinology

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“…Similar to thyroid tumors, promoter hypermethylation in RASSSF1 and APC genes has also been described in parathyroid carcinomas (Juhlin et al 2010, Sulaiman et al 2013. A differential methylation pattern compared with normal parathyroid tissue was observed in parathyroid adenomas (367 genes were significantly altered) and parathyroid carcinomas (175 genes) (Starker et al 2011).…”

Section: Sporadic Endocrine Diseasesmentioning

confidence: 72%

Epigenetic alterations in endocrine-related cancer

Rodríguez-Rodero¹,

Delgado²,

Fernández³

et al. 2014

Endocrine-Related Cancer

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Aberrant epigenetics is a hallmark of cancer, and endocrine-related tumors are no exception. Recent research has been identifying an ever-growing number of epigenetic alterations in both genomic DNA methylation and histone post-translational modification in tumors of the endocrine system. Novel microarray and ultra-deep sequencing technologies have allowed the identification of genome-wide epigenetic patterns in some tumor types such as adrenocortical, parathyroid, and breast carcinomas. However, in other cancer types, such as the multiple endocrine neoplasia syndromes and thyroid cancer, tumor information is limited to candidate genes alone. Future research should fill this gap and deepen our understanding of the functional role of these alterations in cancer, as well as defining their possible clinical uses.

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“…The reverse transcription (RT)-PCR analysis included previously published samples of one normal parathyroid ( Juhlin et al 2010), and four or more parathyroid adenoma samples (Lu et al 2010) for each gene analyzed. Total RNA was extracted using TRIzol reagent (Invitrogen), purified by DNAse I (Amplification Grade, Invitrogen), and quantified by spectrophotometry.…”

Section: Reverse Transcription-pcrmentioning

confidence: 99%