Project description:Approximately 70% of clear cell renal cell carcinoma are characterised by the biallelic inactivation of VHL on chromosome 3p. ELOC-mutated renal cell carcinoma with biallelic ELOC inactivation on chromosome 8q are considered a novel subtype of renal cancer possessing a morphological overlap with ccRCC; however, the frequency and consequences of ELOC alterations in wtVHL and mutVHL is unclear. In this study, we characterise 123 renal tumours with clear cell morphology with known VHL mutation status to assess morphological and molecular consequences of ELOC inactivation. Using Oncoscan and whole exome sequencing we identify 18 ELOC deleted RCC, three of which contain ELOC mutations resulting in the biallelic inactivation of ELOC. Biallelic ELOC and biallelic VHL aberrations were mutually exclusive, although two ELOC-mutated RCC showed monoallelic VHL alterations. Using High Ambiguity Driven Biomolecular Docking we report a novel ELOC variant containing a duplication event disrupting ELOC-pVHL interaction alongside the frequently seen Y79C alteration. Using HRM mass spectrometry we show RCC with biallelic ELOC alterations have significantly reduced ELOC expression but similar CAIX and VEGFA expression when compared to classical ccRCC with VHL inactivation. These data demonstrate that RCC with ELOC and VHL alterations have comparable downstream effects with similar pathways to ccRCC tumourigenesis indicating that both entities are closely related.
Project description:To select signatures of ccRCC, 265 ccRCC samples were obtained from the Van Andel Research Institute. Gene expression profiles of 265 samples were determined using the HG-U133_Plus_2 platform.
Project description:We have sampled several tumour regions from nine clear cell renal cell carcinoma (ccRCC) patients to investigate intra-tumour heterogeneity. We selected 56 tumour samples and 6 normal samples from the 9 patients for expression analysis using microarray data. All samples were fresh frozen upon extraction.
Project description:We have sampled several tumour regions from a single ccRCC patient after 6 weeks everolimus treatment, including both primary and metastatic site samples to investigate intra-tumour heterogeneity.
Project description:We have sampled several tumour regions from a single ccRCC patient after 6 weeks everolimus treatment, including both primary and metastatic site samples to investigate intra-tumour heterogeneity. We selected 8 samples from the primary tumour, and 2 samples from a chestwall metastatic site for expression analysis using microarray data. All samples were fresh frozen upon extraction.
Project description:To identify a therapeutic candidate target molecule for ccRCC, we analyzed the microRNA (miRNA) expression signatures in ccRCC clinical specimens. 9 matched pair (normal tissue and ccRCC tissue) plus 7 ccRCC tissue were analyzed for miRNA-microarray
Project description:We have sampled several tumour regions from nine clear cell renal cell carcinoma (ccRCC) patients to investigate intra-tumour heterogeneity.
