Posterior fossa scintiangiography: documentation of genetic penetrance of von Hippel-Lindau syndrome in a clinically unaffected girl and her father. (41/340)

The 16-year-old clinically normal daughter of a patient with the von Hippel-Lindau syndrome demonstrated a vascular posterior fossa lesion on scintiangiography that failed detection in delayed images. Contrast arteriography corroborated the presence of a hemangioblastoma. Noninvasive demonstration of the genetic penetrance of this disorder offers its victims an opportunity for low morbidity early surgical cure of the associated brain lesions.  (+info)

Clinical and surgical aspects of posterior fossa haemangioblastomata. (42/340)

A retrospective study has been carried out on 67 patients with posterior fossa haemangioblastomata. Clinical details are presented, and the problems of diagnosis discussed. A fresh definition of the von Hippel-Lindau complex is put forward. The results of surgery are good for patients with solitary and sporadic tumours.  (+info)

Percutaneous radio frequency ablation of small renal tumors: initial results. (43/340)

PURPOSE: Thermal tissue ablation with radio frequency energy is an experimental treatment of renal tumor. We report early results of an ongoing trial of percutaneous radio frequency ablation for small renal tumors. MATERIALS AND METHODS: Patients with percutaneously accessible renal tumors were evaluated for radio frequency ablation. Tumors were solid on computerized tomography (CT), 3 cm. or less in diameter and enlarging during at least 1 year. Ablation was performed at the Interventional Radiology suite under ultrasound and/or CT guidance. A 50 W., 460 kHz. electrosurgical generator delivered radio frequency energy via a percutaneously placed 15 gauge coaxial probe. At least 2, 10 to 12-minute ablation cycles were applied to each lesion. Patients were observed overnight before discharge from hospital and reevaluated 2 months later. RESULTS: A total of 24 ablations were performed in 21 patients with renal tumor, including solid von Hippel-Lindau clear cell tumor in 19 and hereditary papillary renal cancer 2. Most (22 of 24) procedures were performed with patients under conscious sedation. At 2 months postoperatively mean tumor diameter plus or minus standard deviation decreased from 2.4 +/- 0.4 to 2.0 +/- 0.5 cm. (p = 0.001), and a majority of tumors (19 of 24, 79%) ceased to be enhanced on contrast CT. Mean serum creatinine plus or minus standard deviation was unchanged during this interval (1.0 +/- 0.2 mg./dl.). No major and 4 minor complications were encountered, including 2 episodes each of transient psoas pain and flank skin numbness. CONCLUSIONS: Percutaneous radio frequency ablation of small renal tumor is well tolerated and minimally invasive. It will remain experimental until procedural and imaging parameters that correlate with tumor destruction are validated.  (+info)

Familial adult renal neoplasia. (44/340)

Our understanding of the molecular mechanisms underlying the tumorigenesis of renal cell carcinoma (RCC) has partially come from studies of RCC related familial cancer syndromes such as von Hippel-Lindau (VHL) disease and hereditary papillary RCC (HPRC). These studies have led to the identification of RCC related genes, which, besides allowing accurate diagnosis of these diseases, have been found mutated or abnormally expressed in the sporadic counterparts of these familial renal tumours. To date, a number of renal tumour related syndromes have been described. We review recent advances in this field and discuss a genetic approach to managing familial cases of renal tumours occasionally encountered by cancer geneticists and urologists.  (+info)

Selective loss of chromosome 11 in pheochromocytomas associated with the VHL syndrome. (45/340)

By using comparative genomic hybridization (CGH), we characterized the genetic profiles of 36 VHL-related pheochromocytomas. We then compared the results with those of sporadic and MEN 2-related pheochromocytomas. In 36 VHL-related tumors, loss of chromosome 3 and chromosome 11 were found in 34 tumors (94%) and 31 tumors (86%), respectively. There was significant concordance of deletions in chromosomes 3 and 11 (Kappa=0.64, P=0.0095), suggesting that they are involved in two different but necessary and complementary genetic pathways. The loss of chromosome 11 appeared to be specific for VHL-related pheochromocytoma as it was not present in any of the 10 VHL-related CNS hemangioblastomas studied and was significantly less common when compared with (a) sporadic pheochromocytomas from previously published results (13%; P=<0.0001), and (b) MEN 2-related pheochromocytomas from this and previously published studies (30%; P=0.0012). In summary, this is the first report of a novel consistent genetic alteration that is selected and specific for VHL-related pheochromocytoma, besides the two hits of the VHL gene.  (+info)

Mutational analysis of the von hippel lindau gene in clear cell renal carcinomas from tuberous sclerosis complex patients. (46/340)

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by seizures, mental retardation, autism, and tumors of multiple organs. Renal disease in TSC includes angiomyolipomas, cysts, and renal cell carcinomas. It is known that somatic mutations in the von Hippel Lindau (VHL) tumor suppressor gene occur in most clear cell renal carcinomas. To determine whether TSC-associated clear cell carcinomas also contain VHL mutations, we analyzed six tumors for loss of heterozygosity in the VHL gene region of chromosome 3p and for mutations in the VHL gene. Four of the patients were women between the ages of 34 and 68 years, and two were males under the age of 21 years. The loss of heterozygosity analysis was performed using polymorphic microsatellite markers, and the mutational analysis was performed using direct sequencing. Chromosome 3p loss of heterozygosity was not detected, and no VHL mutations were identified. These findings suggest that mutations in the TSC1 and TSC2 genes lead to clear cell renal carcinogenesis via an alternate pathway not involving VHL mutations.  (+info)

Disruption of a novel MFS transporter gene, DIRC2, by a familial renal cell carcinoma-associated t(2;3)(q35;q21). (47/340)

Previously, we described a family with a significantly increased predisposition for renal cell cancer co-segregating with a t(2;3)(q35;q21) chromosomal translocation. Several primary tumors of the clear cell type from different family members were analyzed at a molecular level. Loss of the derivative chromosome 3 was consistently found. In addition, different somatic Von Hippel Lindau (VHL) gene mutations were observed in most of the tumors analyzed, even within the same patient. Based on these results a multistep tumorigenesis model was proposed in which (non-disjunctional) loss of the derivative chromosome 3 represents an early event and somatic mutation of the VHL gene represents a late event related to tumor progression. More recently, however, we noted that these two anomalies were absent in at least one early-stage tumor sample that we tested. Similar results were obtained in another family with renal cell cancer and t(3;6)(q12;q15), thus suggesting that another genetic event may precede these two oncogenetic steps. We speculate that deregulation of a gene(s) located at or near the translocation breakpoint may act as such. In order to identify such genes, a detailed physical map encompassing the 3q21 breakpoint region was constructed. Through a subsequent positional cloning effort we found that this breakpoint targets a hitherto unidentified gene, designated DIRC2 (disrupted in renal cancer 2). Computer predictions of the putative DIRC2 protein showed significant homology to different members of the major facilitator superfamily (MFS) of transporters. Based on additional DIRC2 expression and mutation analyses, we propose that the observed gene disruption may result in haplo-insufficiency and, through this mechanism, in the onset of tumor growth.  (+info)

High frequency loss of heterozygosity in von Hippel-Lindau (VHL)-associated and sporadic pancreatic islet cell tumors: evidence for a stepwise mechanism for malignant conversion in VHL tumorigenesis. (48/340)

Germ-line mutation of the von Hippel-Lindau (VHL) gene predisposes to the development of multifocal, benign lesions, including retinal and central nervous system hemangioblastomas, pheochromocytomas, and renal and pancreatic cysts. Progression to malignancy in VHL disease is associated primarily with the development of renal cell carcinoma (RCC) and pancreatic islet cell tumors (PICT). Although many reports have documented the multiple functions of the VHL protein, few have investigated the intriguing question related to the tissue-specificity of malignant conversion in VHL disease, a problem not easily explained by strict genotype-phenotype correlations. We investigated a novel VHL kindred with a preponderance of PICTs to determine whether loss of additional genetic loci associated with the sporadic forms of RCC and PICTs might play a role in malignant conversion in this disease. We report the high frequency loss of heterozygosity (LOH) of genetic loci distinct from and mapping proximal to VHL within human chromosome 3p in the VHL kindred under study. Furthermore, chromosome 3p LOH occurs subsequent to VHL mutation and cyst formation, and correlates with malignant progression in VHL-associated PICTs. High frequency LOH was also observed in sporadic PICTs in regions of 3p associated with LOH in sporadic clear cell RCC as well as homozygous deletion in lung cancer. A stepwise model for malignant conversion in VHL disease is herein proposed.  (+info)