title: Genetic alteration in notch pathway is associated with better prognosis in renal cell carcinoma.
abstract: Notch signaling was associated with a variety of cancers but was not comprehensively studied in clear-cell renal cell carcinoma (ccRCC). We have in this study studied the genetic alteration (mutation and copy number variance) of Notch gene set in the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) database. We found that Notch pathway was frequently altered in ccRCC. The Notch gene set was genetically altered in 182 (44%) of the 415 ccRCC patients. CNV was the predominant type of alteration in most genes. Alterations in KAT2B and MAML1 occurred in 13% and 19% of patients, respectively, both of which were functionally active in ccRCC. Deletion of VHL was exclusively found in cases with Notch alteration. Overall survival was longer in ccRCC patients with altered-Notch pathway. The median survival was 90.41 months in Notch-altered cases and 69.15 in Notch-unaltered cases (P = 0.0404). The median disease free time was 89.82 months in Notch-altered cases and 77.27 months in in Notch-unaltered cases (P = 0.935). Conclusively, Notch signaling was altered in almost half of the ccRCC patients and copy number variances in MAML1 and KAT2B were predominant changes. These findings broadened our understanding of the role of Notch in ccRCC.
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
authors.forename: Zuquan
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
authors.forename: Haowen
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
authors.forename: Zujun
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hui
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D011379:Prognosis; D051880:Receptors, Notch / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D050880:p300-CBP Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D000099224:p300-CBP-Associated Factor
chemical_list: D004268:DNA-Binding Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C430872:MAML1 protein, human
keywords: KAT2B; MAML1; NOTCH; clear cell renal cell carcinoma