|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
|
|
|
|
Malignant neoplasm of kidney
|
0.600 |
CausalMutation
|
disease |
CGI |
|
|
|
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Loss of function mutations in the fumarate hydratase (fumarase, FH) gene were recently identified as the cause for dominantly inherited uterine and cutaneous leiomyomas and renal cell cancer.
|
12183404 |
2002 |
|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
BEFREE |
In addition to VHL, which is associated with clear cell carcinoma, one can now list HPRC (associated with type I papillary renal cancer) and HLRCC (associated with type II papillary renal cancer).
|
14521208 |
2003 |
|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
BEFREE |
Fumarate hydratase, a component of the tricarboxylic acid cycle, acts as a tumor suppressor gene in the development of cutaneous and uterine leiomyoma and renal cell cancer in this syndrome.
|
14632190 |
2003 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
A proportion of individuals with FH mutations have associated renal cancer, a variant known as hereditary leiomyomatosis and renal cell cancer (HLRCC).
|
16029320 |
2005 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Missense FH mutations predisposing to renal cancer had no unusual features, and identical mutations were found in families without renal cancer, suggesting a role for genetic or environmental factors in renal cancer development in MCUL.
|
16237213 |
2005 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Germline mutations in FH predispose individuals to leiomyomas and renal cell cancer (HLRCC), whereas mutations in SDH cause paragangliomas and phaeochromocytomas (HPGL).
|
15987702 |
2005 |
|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
BEFREE |
HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability.
|
16098467 |
2005 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Recent investigations into other hereditary forms of kidney cancer with mutations in genes involving energy metabolism and oxidative changes, such as fumarate hydratase, suggest that metabolic changes related to hypoxia detection may be a common mechanism of tumorigenesis.
|
16364563 |
2006 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Conventional renal cancer in a patient with fumarate hydratase mutation.
|
17270241 |
2007 |
|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
BEFREE |
HIF and fumarate hydratase in renal cancer.
|
17211469 |
2007 |
|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
BEFREE |
In some families renal cell cancer also forms a component of the complex and as such has been described as hereditary leiomyomatosis and renal cell cancer (HLRCC: OMIM 605839).
|
18366737 |
2008 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Although the familial occurrence of these rare tumors might be coincidental, it cannot be ruled out that, beside FH, mutations in another as yet unknown gene could give rise to both leiomyosarcoma and kidney cancer.
|
18986479 |
2008 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Mutation screening of fumarate hydratase by multiplex ligation-dependent probe amplification: detection of exonic deletion in a patient with leiomyomatosis and renal cell cancer.
|
18503824 |
2008 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
However, investigation of the Mendelian single-gene syndromes, like von Hippel Lindau (VHL: VHL gene), hereditary papillary renal carcinoma (HPRC: c-Met gene), Birt-Hogg-Dubé (BHD: BHD gene), and hereditary leiomyomatosis renal cell cancer (HLRCC: fumarate hydratase gene) provides an opportunity to develop pathway specific therapies.
|
19285230 |
2009 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Such aggregation of RCC in only some families and populations has led to the hypothesis that besides FH mutations also other inherited genetic and/or environmental factors may contribute to the malignant kidney tumor formation.
|
20091131 |
2010 |
|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
BEFREE |
Succinate dehydrogenase and fumarate hydratase are mitochondrial proteins of the TCA cycle and the respiratory chain and when mutated lead to tumours of the nervous system known as paragangliomas and pheochromocytomas, and in the case of fumarate hydratase, cutaneous and uterine leiomyomas and renal cell cancer.
|
20304625 |
2010 |
|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
BEFREE |
The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels.
|
21907923 |
2011 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Two FH mutation carriers had papillary type 2 renal cancer and Wilms' tumour, respectively.
|
20618355 |
2011 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
As part of the French National Cancer Institute (INCa) 'Inherited predispositions to kidney cancer' network, sequence analysis and a functional study of FH were preformed in 56 families with clinically proven or suspected HLRCC and in 23 patients with isolated PRCCII (5 familial and 18 sporadic).
|
21398687 |
2011 |
|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
BEFREE |
Several therapeutic approaches for targeting the metabolic basis of FH-deficient kidney cancer are under development or are being evaluated in clinical trials, including the use of agents such as metformin, which would reverse the inactivation of AMPK, approaches to inhibit glucose transport, lactate dehydrogenase A (LDHA), the antioxidant response pathway, the heme oxygenase pathway, and approaches to target the tumor vasculature and glucose transport with agents such as bevacizumab and erlotinib.
|
23633457 |
2013 |
|
Malignant neoplasm of kidney
|
0.600 |
Biomarker
|
disease |
BEFREE |
Fumarate hydratase (FH)-deficient kidney cancer undergoes metabolic remodeling, with changes in mitochondrial respiration, glucose, and glutamine metabolism.
|
23967283 |
2013 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is an autosomal dominant disorder in which germline mutations of fumarate hydratase (FH) gene confer an increased risk of cutaneous and uterine leiomyomas and renal cancer.
|
24441663 |
2014 |
|
Malignant neoplasm of kidney
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Type 1 papillary kidney cancers arise in conjunction with germline mutations in MET and type 2 as part of hereditary leiomyomatosis and kidney cell cancer (fumarate hydratase [FH] mutations).
|
24359990 |
2014 |