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.
"Figure 2: CT image of the solid mass in the left ureteropelvic junction with severe hydronephrosis. chronic irritation, hydronephrosis, and urinary calculi have been the most commonly discussed etiologic factors . The symptoms of the synchronous RCC and TCC are similar to the solitary RCC or TCC of the kidney. "
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: We present a 15-years old young child primarily presented to general surgeon for abdominal mass and gross haematuria. His detailed imaging studies and other relevant investigations revealed that it is a case of Paediatric Renal Cell carcinoma (RCC), which was clinically not associated with any of the known malignancies or syndromes. On detailed histo-pathological examination this was reported as a special type of Pediatric RCC not fitting into clear cell, papillary, chromophobic, oncocytoma, or collecting duct RCC.
Journal of Ayub Medical College, Abbottabad: JAMC 05/2014; 23(2):184-5.
[Show abstract][Hide abstract] ABSTRACT: The epidermal growth factor receptor (EGFR) has frequently been implicated in hyperproliferative diseases of renal tubule epithelia. We have shown that the NF2 tumor suppressor Merlin inhibits EGFR internalization and signaling in a cell contact-dependent manner. Interestingly, despite the paucity of recurring mutations in human renal cell carcinoma (RCC), homozygous mutation of the NF2 gene is found in approximately 2% of RCC patient samples in the Sanger COSMIC database. To examine the roles of Merlin and EGFR in kidney tumorigenesis, we generated mice with a targeted deletion of Nf2 in the proximal convoluted epithelium using a Villin-Cre transgene. All of these mice developed intratubular neoplasia by 3 months, which progressed to invasive carcinoma by 6-10 months. Kidneys from these mice demonstrated marked hyperproliferation and a concomitant increase in label-retaining putative progenitor cells. Early lumen-filling lesions in this model exhibited hyperactivation of EGFR signaling, altered solubility of adherens junctions components, and loss of epithelial polarity. Renal cortical epithelial cells derived from either early or late lesions were dependent on EGF for in vitro proliferation and were arrested by pharmacologic inhibition of EGFR or re-expression of Nf2. These cells formed malignant tumors upon s.c. injection into immunocompromised mice before in vitro passage. Treatment of Vil-Cre;Nf2(lox/lox) mice with the EGFR inhibitor erlotinib halted the proliferation of tumor cells. These studies give added credence to the role of EGFR signaling and perhaps Nf2 deficiency in RCC and describe a rare and valuable mouse model for exploring the molecular basis of this disease.
Proceedings of the National Academy of Sciences 07/2009; 106(24):9767-72. DOI:10.1073/pnas.0902031106 · 9.67 Impact Factor
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