Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas.

Hereditary papillary renal carcinoma (HPRC) is a recently recognized form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumours. The pattern of inheritance of HPRC is consistent with autosomal dominant transmission with reduced penetrance. HPRC is histologically and genetically distinct from two other causes of inherited renal carcinoma, von Hippel-Lindau disease (VHL) and the chromosome translocation (3;8). Malignant papillary renal carcinomas are characterized by trisomy of chromosomes 7, 16 and 17, and in men, by loss of the Y chromosome. Inherited and sporadic clear cell renal carcinomas are characterized by inactivation of b…

Fast, non-toxic, and inexpensive n-butanol preparation of recombinant plasmids

Various commercial and non-commercial plasmid preparation protocols are currently available. However, the kits are expensive and many of the protocols contain toxic chemicals. Here we present a novel, optimized and, therefore, very advantageous plasmid preparation protocol using n-butanol. The preparation can be performed quickly and no toxic chemicals are used, at overall costs of about one cent per plasmid preparation.Atualmente vários protocolos comerciais e não comerciais para preparação de plasmídeos estão disponíveis. Contudo, os kits são caros e muitos dos protocolos contêm substâncias químicas tóxicas. Apresentamos neste trabalho um novo, otimizado e portanto muito vantajoso protoco…

Novel mutations of the MET proto-oncogene in papillary renal carcinomas.

Hereditary papillary renal carcinoma (HPRC) is characterized by multiple, bilateral papillary renal carcinomas. Previously, we demonstrated missense mutations in the tyrosine kinase domain of the MET proto-oncogene in HPRC and a subset of sporadic papillary renal carcinomas. In this study, we screened a large panel of sporadic papillary renal carcinomas and various solid tumors for mutations in the MET proto-oncogene. Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors. We detected five novel missense mutations; three of five mutations were located in the ATP-binding region of t…

von Hippel-Lindau Protein-Mediated Repression of Tumor Necrosis Factor Alpha Translation Revealed through Use of cDNA Arrays

Based on evidence that the von Hippel-Lindau (VHL) tumor suppressor protein is associated with polysomes and interacts with translation regulatory factors, we set out to investigate the potential influence of pVHL on protein translation. To this end, renal cell carcinoma (RCC) cells that either lacked pVHL or expressed pVHL through stable transfection were used to prepare RNA from cytosolic (unbound) and polysome-bound fractions. Hybridization of cDNA arrays using RNA from each fraction revealed a subset of transcripts whose abundance in polysomes decreased when pVHL function was restored. The tumor necrosis factor alpha (TNF-alpha) mRNA was identified as one of the transcripts that prefere…

Clinical utility gene card for: von Hippel-Lindau (VHL).

Childhood-onset CADASIL: clinical, imaging, and neurocognitive features.

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a progressive neurodegenerative condition, associated with mutations in the notch3 gene. Symptoms include migraine with aura, mood disorders, progressive cognitive decline, subcortical ischemic strokes, dementia, and premature death. We present an 8-year-old boy with attention and behavioral difficulties, as well as a family history of the condition. Magnetic resonance imaging revealed subcortical foci of increased T2 hyperintensity, and sequencing of the notch3 gene revealed 1 previously reported mutation and 1 novel sequence variant. Neurocognitive assessment revealed deficits in sever…