caa a22 4500 445331429 CHVBK 20180317142738.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10689-011-9428-z doi (NATIONALLICENCE)springer-10.1007/s10689-011-9428-z Lehtonen Heli Department of Medical Genetics, Genome-Scale Biology Research Program, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00290, Helsinki, Finland aut Hereditary leiomyomatosis and renal cell cancer: update on clinical and molecular characteristics [Elektronische Daten] [Heli Lehtonen] Hereditary leiomyomatosis and renal cell cancer (HLRCC, also known as multiple cutaneous and uterine leiomyomatosis, MCUL) is a highly penetrant autosomal dominant tumor predisposition syndrome characterized by benign leiomyomas of the skin and the uterus. Renal cell carcinomas, occurring in a subset of the HLRCC families, are exceptionally aggressive. Therefore careful, frequent surveillance strategies are recommended. Association of malignant smooth-muscle tumors, leiomyosarcomas, with HLRCC has been observed but the risk appears to be smaller than initially estimated. To date inactivating heterozygous mutations in the fumarate hydratase (FH, fumarase) gene, predisposing to HLRCC, have been found in approximately 180 families worldwide. The most extensively studied hypothesis on molecular mechanisms of HLRCC tumorigenesis is activation of the hypoxia pathway due to aberrant stabilization of the HIF1 transcription factor. HIF1 regulates transcription of genes relevant for vascularization, glucose transport and glycolysis, processes that facilitate tumor growth. However, additional mechanisms underlying tumor formation are likely to exist. Springer Science+Business Media B.V., 2011 Fumarate hydratase (FH) nationallicence HIF1 nationallicence HLRCC nationallicence Kidney nationallicence Leiomyoma nationallicence Leiomyosarcoma nationallicence MCUL nationallicence Renal cell cancer nationallicence Tricarboxylic acid cycle nationallicence α-KG : α-ketoglutarate nationallicence CDC : Collecting duct carcinoma nationallicence CLM : Cutaneous leiomyoma nationallicence FH : Fumarate hydratase nationallicence FHD : Fumarate hydratase deficiency nationallicence FIH : Factor inhibiting HIF nationallicence HIF1 : Hypoxia inducible factor 1 nationallicence HLRCC : Hereditary leiomyomatosis and renal cell cancer nationallicence HPRC : Hereditary papillary renal carcinoma nationallicence GLUT1 : Glucose transporter 1 nationallicence LDHA : Lactate dehydrogenase A nationallicence LOH : Loss of heterozygosity nationallicence MCUL : Multiple cutaneous and uterine leiomyomatosis nationallicence MLPA : Multiplex ligation-dependent probe amplification nationallicence MRI : Magnetic resonance imaging nationallicence PET-CT : Positron emission tomography-computed tomography nationallicence PHD : Prolyl hydroxylase domain protein nationallicence RCC : Renal cell cancer nationallicence SDHA/B/C/D : Succinate dehydrogenase subunit A, B, C or D nationallicence TCA cycle : Tricaboxylic acid cycle nationallicence ULM : Uterine leiomyoma nationallicence ULMS : Uterine leiomyosarcoma nationallicence VEGFA : Vascular endothelial growth factor A nationallicence VEFGR : Vascular endothelial growth factor receptor nationallicence VHL : Von Hippel Lindau syndrome nationallicence Familial Cancer Springer Netherlands 10/2(2011-06-01), 397-411 1389-9600 10:2<397 2011 10 10689 https://doi.org/10.1007/s10689-011-9428-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-011-9428-z text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Lehtonen Heli Department of Medical Genetics, Genome-Scale Biology Research Program, Biomedicum Helsinki, Haartman Institute, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00290, Helsinki, Finland aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/2(2011-06-01), 397-411 1389-9600 10:2<397 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer