Genetics and molecular biology of renal cancer

2017 ◽  
Author(s):  
Mariam Jafri ◽  
Eamonn R Maher
Keyword(s):  
Clinical Features ◽  
Kidney Cancer ◽  
Renal Cancer ◽  
Cancer Syndrome ◽  
Inherited Disorders ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Molecular Pathophysiology ◽  
Cancer Syndromes ◽  
Key Pathways

Renal cell carcinoma (RCC) is the exemplar of how the understanding of the molecular pathogenesis of rare inherited disorders can inform an understanding of the key pathways involved in the pathogenesis of sporadic cancer. In this chapter we describe the clinical and pathological features of the inherited kidney cancer syndromes: von Hippel Lindau disease (VHL); Birt-Hogg-Dube syndrome; hereditary leiomyomatosis and renal cancer syndrome; succinate dehydrogenase disorders; hereditary papillary renal cancer; and translocation-associated kidney cancer. Though individually rare, recognition of individuals with familial kidney cancer is important as they present specific clinical challenges to the urological surgeon because of their propensity to develop multicentric/bilateral tumours. Furthermore, different familial RCC predisposition syndromes are associated with different extra renal clinical features and have specific surveillance needs. Despite differences in clinical features, there is some overlap in the molecular pathophysiology between the disorders and these highlight the key signalling pathways for RCC oncogenesis.

Phase II study of pazopanib in patients with von Hippel-Lindau disease.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4516-4516 ◽  
Author(s):  
Eric Jonasch ◽  
Dan S. Gombos ◽  
Steven G. Waguespack ◽  
Valerie Marcott ◽  
Diane D Liu ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Clinical Features ◽  
Surgical Intervention ◽  
Standards Of Care ◽  
Common Side Effect ◽  
Drug Discontinuation ◽  
Best Interest ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Vhl Disease

4516 Background: Von Hippel-Lindau disease (VHL) is an autosomal dominant inherited disorder. Affected individuals develop vascular neoplastic lesions in multiple sites including eye, brain, pancreas, adrenal and kidney. Standards of care include surveillance imaging and surgical intervention. We hypothesized that treatment of VHL related lesions with an antiangiogenic agent would result in shrinkage of all lesion types. We chose the multikinase inhibitor pazopanib to test this hypothesis. Methods: After obtaining IRB approval, patients with clinical features or genetic confirmation of VHL disease and with measurable lesions were treated with pazopanib 800mg PO daily for two 12-week cycles. Efficacy was determined by RECIST after two cycles. Patients had the option to continue therapy if considered in patient’s best interest. Continuous monitoring for any lesion progression and drug discontinuation due to toxicity during the whole period of the treatment was planned. Results: Patients were enrolled (N=32) and treated (N=31) between 1/2012 and 6/2016. Median age was 37 (range 19-67). 23 patients had genomically confirmed VHL disease; four had family and personal history but had not undergone genetic testing, and five patients had clinical features of VHL disease and negative genetic testing. A median of two cycles (range 1-12) of therapy was administered. Of 31 evaluable patients, 13 (42%) showed a response, 18 patients had stable disease and no patients had PD as best response. Responses were seen in renal (2 CR and 29 PR/59 total), pancreatic (9 PR/17 total) and CNS 2 PR/49 total) target lesions. The most common side effect was diarrhea (grades 1 and 2) experienced in 14 patients. Twelve patients dose reduced to 600 mg and 6 to 400 mg pazopanib PO daily. Eight patients discontinued therapy due to adverse events of whom 4 experienced transaminitis. One patient experienced a grade V CNS hemorrhage. Conclusions: This is the largest prospective VHL disease specific therapeutic study performed to date. Pazopanib resulted in significant and sustained disease control for the majority of VHL patients enrolled on the study, with an acceptable safety profile. This agent may be considered as an alternative to surgical intervention in patients with VHL disease. Clinical trial information: NCT01436227.

Clinical Features and Natural History of von Hippel-Lindau Disease

QJM ◽  
1990 ◽  
Vol 77 (2) ◽  
pp. 1151-1163 ◽  
Author(s):  
E. R. MAHER ◽  
J. R. W. YATES ◽  
R. HARRIES ◽  
C. BENJAMIN ◽  
R. HARRIS ◽  
...  
Keyword(s):  
Natural History ◽  
Clinical Features ◽  
Von Hippel Lindau ◽  
History Of ◽  
Von Hippel Lindau Disease

Renal cancer in von Hippel–Lindau disease and related syndromes

2013 ◽  
Vol 9 (9) ◽  
pp. 529-538 ◽  
Author(s):  
Birke Bausch ◽  
Cordula Jilg ◽  
Sven Gläsker ◽  
Alexander Vortmeyer ◽  
Niklas Lützen ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease

95 Management of renal cancer in a contemporary series of patients affected by Von Hippel-Lindau disease

2013 ◽  
Vol 12 (1) ◽  
pp. e95-e96 ◽  
Author(s):  
P. Destefanis ◽  
B. Lucatello ◽  
M. Maccario ◽  
A. Veltri ◽  
B. Pasini ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease

scholarly journals Preimplantation genetic diagnosis of Von Hippel-Lindau disease cancer syndrome by combined mutation and segregation analysis

2007 ◽  
Vol 30 (2) ◽  
pp. 330-335
Author(s):  
Denilce R. Sumita ◽  
José Cláudio C. Rocha ◽  
Assumpto Iaconelli Jr. ◽  
Edson Borges Jr. ◽  
Lygia V. Pereira
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Segregation Analysis ◽  
Genetic Diagnosis ◽  
Cancer Syndrome ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease

scholarly journals Supratentorial hemangioblastoma: clinical features, prognosis, and predictive value of location for von Hippel-Lindau disease

2012 ◽  
Vol 14 (8) ◽  
pp. 1097-1104 ◽  
Author(s):  
S. A. Mills ◽  
M. C. Oh ◽  
M. J. Rutkowski ◽  
M. E. Sughrue ◽  
I. J. Barani ◽  
...  
Keyword(s):  
Clinical Features ◽  
Predictive Value ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease

scholarly journals Large deletion causing von Hippel-Lindau disease and hereditary breast cancer syndrome

2014 ◽  
Vol 12 (1) ◽  
Author(s):  
Karol Krzystolik ◽  
Anna Jakubowska ◽  
Jacek Gronwald ◽  
Maciej R Krawczyński ◽  
Monika Drobek-Słowik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Large Deletion ◽  
Cancer Syndrome ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease

Clinical features of patients bearing central nervous system hemangioblastoma in von Hippel-Lindau disease

2012 ◽  
Vol 155 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Hiroshi Kanno ◽  
Jun-ichi Kuratsu ◽  
Ryo Nishikawa ◽  
Kazuhiko Mishima ◽  
Atushi Natsume ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Features ◽  
Von Hippel Lindau ◽  
Von Hippel Lindau Disease ◽  
Central Nervous System Hemangioblastoma

scholarly journals Evaluation of the safety and effectiveness of oral propranolol in patients with von Hippel-Lindau disease and retinal hemangioblastomas: phase III clinical trial

2019 ◽  
Vol 4 (1) ◽  
pp. e000203 ◽  
Author(s):  
Beatriz González-Rodríguez ◽  
Karina Villar Gómez de las Heras ◽  
Daniel T Aguirre ◽  
Luis Rodríguez-Padial ◽  
Virginia Albiñana ◽  
...  
Keyword(s):  
Disease Activity ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Cancer Syndrome ◽  
Von Hippel Lindau ◽  
Long Term Effect ◽  
Registration Number ◽  
Von Hippel Lindau Disease ◽  
Vhl Disease ◽  
Endothelial Growth Factor

Backgroundvon Hippel-Lindau disease (VHL) is a multisystem cancer syndrome caused by mutations in the VHL gene. Retinal hemangioblastoma is one of the most common tumours, and when it appears near the optic nerve, its treatment is challenging and risky. To date, no treatment has proven effective in changing the course of the disease. This study was designed to evaluate the safety and effectiveness of propranolol in controlling these tumours.MethodsSeven patients were included. All patients took a daily dose of 120 mg of propranolol for 1 year. Clinical variables were assessed at baseline, and at 1, 3, 6, 9 and 12 months. The primary endpoint of the study was the number and size of retinal hemangioblastomas. On every visit, retinal outcomes and blood biomarkers (such as vascular endothelial growth factor (VEGF) and miR210) were analysed.ResultsNumber and size of retinal hemangioblastomas remained stable in all patients. All of them had initially increased levels of VEGF and miR210. There was a gradual reabsorption of retinal exudation in two patients, correlating with a progressive decrease of both biomarkers. The only adverse effect reported was hypotension in one patient.ConclusionsPropranolol could be used to treat retinal hemangioblastomas in VHL patients, although more studies are needed to determine the ideal dose and long-term effect. VEGF and miR210 should be explored as biomarkers of disease activity. As far as we know, these are the first biomarkers proposed to monitor the VHL disease activity.Trial registration number2014-003671-30

Sign in / Sign up

Export Citation Format

Share Document