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Sato, Yusuke; Yoshizato, Tetsuichi; Shiraishi, Yuichi; Maekawa, Shigekatsu; Okuno, Yusuke; Kamura, Takumi; Shimamura, Teppei; Sato-Otsubo, Aiko; Nagae, Genta; Suzuki, Hiromichi; Nagata, Yasunobu; Yoshida, Kenichi; Kon, Ayana; Suzuki, Yutaka; Chiba, Kenichi; Tanaka, Hiroko; Niida, Atsushi; Fujimoto, Akihiro; Tsunoda, Tatsuhiko; Morikawa, Teppei; Maeda, Daichi; Kume, Haruki; Sugano, Sumio; Fukayama, Masashi; Aburatani, Hiroyuki; Sanada, Masashi; Miyano, Satoru; Homma, Yukio; Ogawa, Seishi
Nature genetics, 08/2013, Letnik: 45, Številka: 8Journal Article
Clear-cell renal cell carcinoma (ccRCC) is the most prevalent kidney cancer and its molecular pathogenesis is incompletely understood. Here we report an integrated molecular study of ccRCC in which ≥100 ccRCC cases were fully analyzed by whole-genome and/or whole-exome and RNA sequencing as well as by array-based gene expression, copy number and/or methylation analyses. We identified a full spectrum of genetic lesions and analyzed gene expression and DNA methylation signatures and determined their impact on tumor behavior. Defective VHL-mediated proteolysis was a common feature of ccRCC, which was caused not only by VHL inactivation but also by new hotspot TCEB1 mutations, which abolished Elongin C-VHL binding, leading to HIF accumulation. Other newly identified pathways and components recurrently mutated in ccRCC included PI3K-AKT-mTOR signaling, the KEAP1-NRF2-CUL3 apparatus, DNA methylation, p53-related pathways and mRNA processing. This integrated molecular analysis unmasked new correlations between DNA methylation, gene mutation and/or gene expression and copy number profiles, enabling the stratification of clinical risks for patients with ccRCC.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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