Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC, all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis. On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative or focally positive for MET expression. In clear cell RCC, MET expression was positively correlated with high nuclear grade, presence of infiltrative growth, tumoral necrosis, papillary architecture, sarcomatoid component, tumoral involvement of the renal pelvis or ureter, involvement of the calyx, and lymphatic invasion. In conclusion, diffuse and strong expression of MET in papillary RCC and collecting duct carcinoma might be helpful in discriminating from the other subtypes of RCC with tubular or papillary growth. In case of MET expression observed in clear cell RCC, it might correlate with those clinicopathological parameters implying aggressive behavior.
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PMID:MET expression in sporadic renal cell carcinomas. 1689 11

Renal cell carcinoma (RCC) accounts for approximately 3% of all new cancer diagnosis every year. RCC arises from the renal epithelium and represents 85% of all kidney tumors. According to histology, these neoplasms are divided into the following types: clear cell, papillary, chromophobe, oncocytoma, collecting duct, and unclassified. Approximately, 75% of RCCs are of the clear cell type and in recent years, there have been substantial advances in the understanding of its molecular biology leading to the development of effective treatments. However, there is still an area of uncertainty with regard to non-clear cell histologies. Scarce studies have been conducted testing different drugs in this patient population. Thus, most of the evidence comes from small phase II trials, retrospective analysis, or expanded access programs. Recent insights in the molecular basis of these tumors have opened a promising research field. Molecules targeting mammalian target of rapamycin, epidermal growth factor receptor, c-MET, vascular endothelial growth factor, and platelet-derived growth factor are among some of the promising drugs tested in this setting. This article reviews the mechanisms of disease on RCC and summarizes treatment options with a particular focus on patients with non-clear cell tumors.
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PMID:Non-clear cell advanced kidney cancer: is there a gold standard? 2117 5

Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease.
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PMID:Genetic basis of kidney cancer: role of genomics for the development of disease-based therapeutics. 2303 66

The non-clear cell renal cell carcinomas (nccRCCs) are a diverse group of rare-variant renal carcinomas. Each subtype harbors a distinct cell of origin and exhibits a distinct clinical behavior and response to therapy. The advent of next-generation sequencing has drastically advanced our understanding of key genetic and epigenetic drivers in these tumors, although mechanistic studies are needed to elucidate pathogenesis. The only 2 randomized clinical trials in nccRCC included patients with diverse histologic subtypes. Both of these trials compared everolimus with sunitinib and provided evidence suggesting that frontline sunitinib is superior to everolimus in terms of progression-free survival. Renal medullary and collecting duct carcinomas do not respond to targeted agents, supporting the use of platinum-based chemotherapy as frontline therapy. Clinical evidence is currently emerging on the efficacy of c-MET inhibitors in patients with papillary type 1 RCC harboring germline c-MET mutations. Data on the activity of immune checkpoint inhibitors in this setting are lacking; however, several trials are ongoing in this space. The management of patients with nccRCC likely will improve in the future with histology-driven trials, which may pave the way for personalized therapies based on the molecular characterization of these orphan kidney cancer subtypes. Efforts must also be made to establish in vitro and animal models for testing hypotheses generated through extensive genomic analysis. Ultimately, collaborative national and international studies are urgently needed to improve therapeutic strategies in patients with metastatic disease.
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PMID:Non-clear cell renal cell carcinomas: biological insights and therapeutic challenges and opportunities. 2859 Oct 94

Non-clear cell renal cell carcinomas (RCCs) account for up to 25% of kidney cancers and encompass distinct diseases with distinct pathologic features, different molecular alterations, and various patterns of response to systemic therapies. Recent advances in molecular biology and large collaborative efforts helped to better define the oncogenic mechanisms at play in papillary, chromophobe, collecting duct, medullary, translocation, and sarcomatoid RCCs. Papillary RCCs are divided into several subsets of tumors characterized by distinct gene expression profiles, chromatin remodeling genes, cell cycle changes, and alterations of the MET pathway. Chromophobe RCC genomic analysis revealed mostly metabolic pathway alterations with mitochondrial dysfunctions. Translocation RCCs are characterized by MITF fusions and wide genomic reprogramming. Collecting duct carcinomas are distinct entities from upper tract urothelial carcinomas associated with high T-cell infiltration and metabolic alterations. Medullary RCCs present alterations of the INI1 gene and rhabdoid features at pathologic analysis. Finally, sarcomatoid RCCs represent sarcomatoid differentiation for any subsets of RCCs with specific alterations associated with mesenchymal dedifferentiation. From the standpoint of systemic therapy, more than a decade of using VEGF and mTOR inhibitors showed that they generally had limited efficacy in non-clear cell RCCs compared with clear cell RCCs. MET inhibitors are actively being developed for papillary RCC with a specific focus on MET-driven tumors. Other strategies under investigation include CDK4/6 inhibitors in tumors with cell cycle alterations and EZH2 inhibitors in RCCs with INI1 loss. The emergence of immune checkpoint inhibitors and combination strategies enlarges the spectrum of investigational treatments. Better understanding of driver and passenger alterations and better patient stratification along with dedicated clinical networks will be key to improving the management of these rare tumors.
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PMID:Non-Clear Cell Renal Cell Carcinomas: From Shadow to Light. 3037 89

End-stage renal disease (ESRD) patients on dialysis therapy have a higher incidence of renal cell carcinomas (RCCs), which consist of 2 major histopathological types: clear-cell RCCs (ESRD-ccRCCs) and acquired cystic disease (ACD)-associated RCCs. However, their genetic and epigenetic alterations are still poorly understood. Here, we investigated somatic mutations, copy number alterations (CNAs), and DNA methylation profiles in 9 ESRD-ccRCCs and 7 ACD-associated RCCs to identify their molecular alterations and cellular origins. Targeted sequencing of 409 cancer-related genes, including VHL, PBRM1, SETD2, BAP1, KDM5C, MET, KMT2C (MLL3), and TP53, showed ESRD-ccRCCs harbored frequent VHL mutations, while ACD-associated RCCs did not. CNA analysis showed that ESRD-ccRCCs had a frequent loss of chromosome 3p while ACD-associated RCCs had a gain of chromosome 16. Beadarray methylation analysis showed that ESRD-ccRCCs had methylation profiles similar to those of sporadic ccRCCs, while ACD-associated RCCs had profiles similar to those of papillary RCCs. Expression analysis of genes whose expression levels are characteristic to individual segments of a nephron showed that ESRD-ccRCCs and ACD-associated RCCs had high expression of proximal tubule cell marker genes, while chromophobe RCCs had high expression of distal tubule cell/collecting duct cell marker genes. In conclusion, ESRD-ccRCCs and ACD-associated RCCs had mutation and methylation profiles similar to those of sporadic ccRCCs and papillary RCCs, respectively, and these 2 histopathological types of RCCs were indicated to have originated from proximal tubule cells of the nephron.
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PMID:Genetic and epigenetic profiling indicates the proximal tubule origin of renal cancers in end-stage renal disease. 3286 Mar 4