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Davis, Caleb F.; Ricketts, Christopher J.; Wang, Min; Kim, Sang Cheol; Hacker, Kathryn E.; Bhanot, Gyan; Gordenin, Dmitry A.; Biehl, Michael; Kaipparettu, Benny A.; Donehower, Lawrence A.; Tamboli, Pheroze; Hsieh, James J.; Hakimi, A. Ari; Creighton, Chad J.; Davis, Caleb F.; Morgan, Margaret; Donehower, Lawrence A.; Wheeler, David A.; Cherniack, Andrew D.; Choueiri, Toni K.; Kwiatkowski, David J.; Hakimi, A. Ari; Ricketts, Christopher; Rathmell, W. Kimryn; Smith, Angela B.; Wallen, Eric M.; Muzny, Donna; Xi, Liu; Reid, Jeffrey G.; Downs, Brittany; Doddapaneni, Harsha; Lewis, Lora; English, Adam; Meng, Qingchang; Kovar, Christie; Hale, Walker; Sougnez, Carrie; Getz, Gad; Beroukhim, Rameen; Gabriel, Stacey B.; Balasundaram, Miruna; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Lee, Darlene; Lim, Emilia; Sipahimalani, Payal; Thiessen, Nina; Jones, Steven J.M.; Hoadley, Katherine A.; Mieczkowski, Piotr A.; Roach, Jeffrey; Wu, Junyuan; Hoyle, Alan P.; Balu, Saianand; Hayes, D. Neil; Bootwalla, Moiz S.; Chen, Fengju; Noble, Michael S.; DiCara, Daniel; Zou, Lihua; Chin, Lynda; Protopopov, Alexei; Song, Xingzhi; Lee, Eunjung; Luquette, Lovelace J.; Lee, Semin; Xu, Andrew W.; Kucherlapati, Raju; Park, Peter J.; Fargo, David; Choi, Yoon-La; Lee, June-Koo; Akbani, Rehan; Weinstein, John N.; Haussler, David; Lichtenberg, Tara M.; Leraas, Kristen M.; Kaelin, William G.; Vocke, Cathy; Worrell, Robert; Merino, Maria; Spellman, Paul T.; Cheville, John; Baboud, Julien; Velaga, Sudhakar; Liu, Jia; Chudamani, Sudha; Wu, Ye; Sheth, Margi; Mills Shaw, Kenna R.; Yang, Liming; Wang, Zhining; Hutter, Carolyn M.; Sofia, Heidi J.; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A. Gordon; Kwiatkowski, David J.; Park, Peter J.
Cancer cell, 09/2014, Letnik: 26, Številka: 3Journal Article
We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations. •Comprehensive molecular analysis is performed on 66 kidney chromophobe cases•Global molecular patterns provide clues as to this cancer’s cell of origin•mtDNA sequencing reveals loss-of-function mutations in NADH dehydrogenase subunits•Genomic structural rearrangements involving TERT promoter region are assessed Davis et al. describe the landscape of somatic genomic alterations of chromophobe renal cell carcinomas, showing that changes in mitochondrial function are an inherent component of the disease biology and identifying genomic rearrangement as a mechanism for elevated TERT expression.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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