title: Histone modifications: implications in renal cell carcinoma.
abstract: In 2012, an estimated 64,770 men and women were diagnosed with malignancy of the kidney and renal pelvis, of which 13,570 succumbed to their disease. Common genetic aberrations in renal cell carcinomas (RCCs) include loss of function of the VHL gene in clear-cell RCC, overexpression of the c-MET gene in papillary RCC type I, deficiency in the FH gene in papillary RCC type II and loss of heterozygozity of the BHD gene in chromophobe RCC. Recent studies illustrate epigenetic silencing of VHL, as well as alterations in histone modifications and their governing enzymes. The possibility of reversing these epigenetic marks has resulted in efforts to target these changes by utilizing inhibitors of HDACs, DNA methyltransferases and, recently, histone methyltransferases in preclinical and clinical studies. This article focuses on potential therapeutic interventions, and the implications of histone modifications and related enzyme alterations in RCC.
authors.affiliation: Roswell Park Cancer Institute, Department of Cancer Pathology & Prevention, Grace Cancer Drug Center, Buffalo, NY, USA.
authors.forename: Swathi
authors.initials: S
authors.lastname: Ramakrishnan
authors.forename: Leigh
authors.initials: L
authors.lastname: Ellis
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
mesh_terms: D000107:Acetylation; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D056466:Histone Demethylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D056466:Histone Demethylases; D008780:Methyltransferases; D051548:Histone Acetyltransferases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D019859:Proto-Oncogene Proteins c-met; C497446:VHL protein, human
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