Functional epigenomics approach to identify methylated candidate tumour suppressor genes in renal cell carcinoma

Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after treatment with the demethylating agent 5-azacytidine. This enabled us to identify HAI-2/SPINT2 as a novel epigenetically inactivated candidate RCC TSG. To identify further candidate TSGs, we undertook bioinformatic and molecular genetic evaluation of a further 60 genes differentially expressed after demethylation. In addition to HAI-2/SPINT2, four genes (PLAU, CDH1, IGFB3 and MT1G) had previously been shown to undergo promoter methylation in RCC. After bioinformatic prioritisation, expression and/or methylation analysis of RCC cell lines±primary tumours was performed for 34 genes. KRT19 and CXCL16 were methylated in RCC cell lines and primary RCC; however, 22 genes were differentially expressed after demethylation but did not show primary tumour-specific methylation (methylated in normal tissue (n=1); methylated only in RCC cell lines (n=9) and not methylated in RCC cell lines (n=12)). Re-expression of CXCL16 reduced growth of an RCC cell line in vitro. In a summary, a functional epigenomic analysis of four RCC cell lines using microarrays representing 11 000 human genes yielded both known and novel candidate TSGs epigenetically inactivated in RCC, suggesting that this is valid strategy for the identification of novel TSGs and biomarkers

Primary localized laryngeal amyloidosis presenting with hoarseness and dysphagia: A case report

Introduction. Primary localized laryngeal amyloidosis is an extremely rare condition. It usually presents with hoarseness, pain and/or difficulty in breathing. Case presentation. We present the case of a 23-year-old woman with primary localized laryngeal amyloidosis who presented with hoarseness and dysphagia. Conclusion. A search of PubMed shows that dysphagia in patients with laryngeal amyloidosis has been reported only once, although this symptom is relatively common in other conditions presenting with laryngeal mass. There were no signs of any systemic disease in our patient and diagnosis was established histopathologically. She was treated surgically by microlaryngoscopy under general anesthesia and the mass was excised using a CO2 laser technology method. © 2009 Yiotakis et al.; licensee Cases Network Ltd