Renal cancer is resistant to conventional chemotherapy and radiotherapy but increased understanding of the underlying tumour biology is leading to the use and development of targeted therapies, such as tyrosine kinase inhibitors targeting pathways downstream of the von Hippel Lindau tumour suppressor gene.
VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of kidney cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E).
Clear cell renal cell carcinoma (ccRCC) is the major subtype of kidney cancer that is characterized by frequent inactivation of the von Hippel-Lindau (VHL) gene in 80-90% of the tumors.
Clear-cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel-Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of genes that contribute to tumor growth and metastasis, including transforming growth factor-alpha (TGF-alpha), a ligand of the epidermal growth factor receptor (EGFR) tyrosine kinase.
Disease-free survival curves of Kif11 with different cancers and the relationships between Kif11 and the von Hippel-Lindau disease tumour suppressor gene (<i>VHL</i>), and proliferating cell nuclear antigen (PCNA) in kidney cancer were further analysed using the GEPIA database.
In addition to VHL, which is associated with clear cell carcinoma, one can now list HPRC (associated with type I papillary renal cancer) and HLRCC (associated with type II papillary renal cancer).
In conclusion, unlike other hereditary kidney cancer-related genes (i.e., VHL and MET), which are cell type-specific, BHD is involved in the entire spectrum of histological types of renal tumors, suggesting its major role in kidney cancer tumorigenesis.
In this study, we collected 35 archived Swedish sporadic RCCs identified from an epidemiological study on occupational exposure and kidney cancer to test how well stored pathological specimens could be retrieved and analyzed for VHL mutations.
Inactivation of the von Hippel-Lindau tumor suppressor protein (pVHL) causes the most common form of kidney cancer. pVHL is part of a complex that polyubiquitinates the alpha subunit of the heterodimeric transcription factor HIF.
Inactivation of the von Hippel-Lindau tumor suppressor protein (pVHL) is the signature lesion in the most common form of kidney cancer, clear cell renal cell carcinoma (ccRCC). pVHL loss causes the transcriptional activation of hypoxia-inducible factor (HIF) target genes, including many genes that encode histone lysine demethylases.
It exhibits a different molecular signature than clear-cell carcinoma and is typically not associated with mutations in the VHL (von Hippel-Lindau) tumor suppressor gene. pRCC is less responsive to modern drugs introduced in the management of kidney cancer in the past decade.
Loss of VHL function causes the overexpression of transforming growth factor (TGF)-alpha, leading us to hypothesize that TGF-alpha could be a potential TAA for immunotherapy of kidney cancer, which was evaluated in this study.
Most of what is known about the genetic basis of kidney cancer has been learned from study of the inherited forms of kidney cancer: von Hippel Lindau (VHL gene), hereditary papillary renal carcinoma (c-Met gene), Birt Hogg Dubé (BHD gene), and hereditary leiomyomatosis renal cell cancer (fumarate hydratase gene).
pVHL, the product of the VHL tumor suppressor gene, plays an important role in the regulation of cell growth and differentiation of human kidney cells, and inactivation of the VHL gene is the most frequent genetic event in human kidney cancer.