Origin of renal cell carcinomas.
ABSTRACT Cancer is a heritable disorder of somatic cells: environment and heredity are both important in the carcinogenic process. The primal force is the "two hits" of Knudson's hypothesis, which has proved true for many tumours, including renal cell carcinoma. Knudson et al. [1, 2] recognised that familial forms of cancer might hold the key to the identification of important regulatory elements known as tumour-suppressor genes. Their observations (i.e., that retinoblastoma tend to be multifocal in familial cases and unifocal in sporadic presentation) led them to propose a two-hit theory of carcinogenesis. Furthermore, Knudson postulated that patients with the familial form of the cancer would be born with one mutant allele and that all cells in that organ or tissue would be at risk, accounting for early onset and the multifocal nature of the disease. In contrast, sporadic tumours would develop only if a mutation occurred in both alleles within the same cell, and, as each event would be expected to occur with low frequency, most tumours would develop late in life and in a unifocal manner [3, 4]. The kidney is affected in a variety of inherited cancer syndromes. For most of them, both the oncogene/tumour-suppressor gene involved and the respective germline mutations have been identified. Each of the inherited syndromes predisposes to distinct types of renal carcinoma. Families with hereditary predisposition to cancer continue to provide a unique opportunity for the identification and characterisation of genes involved in carcinogenesis. A surprising number of genetic syndromes predispose to the development of renal cell carcinoma, and genes associated with five of these syndromes have been already identified: VHL, MET, FH, BHD and HRPT2. Few cancers have as many different types of genetic predisposition as renal cancer, although to date only a small proportion of renal cell cancers can be explained by genetic predisposition.
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ABSTRACT: To investigate levels of S100A4 protein in plasma and S100A4 mRNA in tumours from patients with clear cell renal cell carcinoma (CCRCC), and correlate these with metastasis, survival and levels of vascular endothelial growth factor (VEGF). Plasma S100A4 and VEGF protein concentrations were measured using enzyme-linked immuno sorbent assays in 39 healthy subjects and 68 consecutive patients with untreated CCRCC. Levels of S100A4 and VEGF mRNA in tumour and matched control (healthy) tissue samples were measured using realtime quantitative reverse transcription- polymerase chain reaction. Findings were analysed with respect to clinico pathological characteristics. Plasma VEGF concentrations were higher in patients with CCRCC than in healthy subjects. S100A4 and VEGF mRNA levels were up-regulated in CCRCC tumour tissue compared with control tissue samples. Logistic regression analysis revealed that up-regulated tumour S100A4 and VEGF mRNA levels were independent risk factors for the presence of invasion and/or metastasis. S100A4 and VEGF are associated with tumour invasion and metastasis, and may be useful prognostic markers in patients with CCRCC. S100A4 and VEGF may represent potential targets for therapeutic intervention.The Journal of international medical research 01/2012; 40(2):475-85. · 0.96 Impact Factor
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ABSTRACT: A 73-year-old man was admitted to our clinic with flank pain and gross macroscopic hematuria. Radiologic examination revealed a solid mass in the left kidney and additionally another mass in the ureteropelvic junction of the same kidney with severe hydronephrosis. Left nephroureterectomy with bladder cuff removel was performed, and histopathological evolution showed a Fuhrman grade 3 clear cell type RCC with low-grade TCC of the pelvis.Case reports in urology. 01/2013; 2013:194127.
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ABSTRACT: The mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development, maintenance, and regeneration. We show that the adult mammalian kidney undergoes continuous tubulogenesis via expansions of fate-restricted clones. Kidneys recovering from damage undergo tubulogenesis through expansions of clones with segment-specific borders, and renal spheres developing in vitro from individual cells maintain distinct, segment-specific fates. Analysis of mice derived by transfer of color-marked embryonic stem cells (ESCs) into uncolored blastocysts demonstrates that nephrons are polyclonal, developing from expansions of singly fated clones. Finally, we show that adult renal clones are derived from Wnt-responsive precursors, and their tracing in vivo generates tubules that are segment specific. Collectively, these analyses demonstrate that fate-restricted precursors functioning as unipotent progenitors continuously maintain and self-preserve the mouse kidney throughout life.Cell reports. 05/2014;