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Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma
- Source :
- Cell Reports, Vol 14, Iss 10, Pp 2476-2489 (2016), Cell Reports, vol. 14, no. 10, pp. 2476-2489
- Publication Year :
- 2016
- Publisher :
- Elsevier, 2016.
-
Abstract
- On the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy number, and RNA and protein expression), we classified 894 renal cell carcinomas (RCCs) of various histologic types into nine major genomic subtypes. Site of origin within the nephron was one major determinant in the classification, reflecting differences between clear cell, chromophobe, and papillary RCC. Widespread molecular changes associated with chromatin modifier genes or TFE3 gene fusion were present within specific subtypes as well as spanning multiple subtypes. Differences in patient survival and in alteration of specific pathways—including hypoxia, metabolism, MAP kinase, NRF2-ARE, Hippo, immune checkpoint, and PI3K/AKT/mTOR—could further distinguish the subtypes. Immune checkpoint markers and molecular signatures of T cell infiltrates were both highest in the subtype associated with aggressive clear cell RCC. Differences between the genomic subtypes suggest that therapeutic strategies could be tailored to each RCC disease subset.
- Subjects :
- 0301 basic medicine
Chromophobe cell
Biology
Bioinformatics
urologic and male genital diseases
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
Phosphatidylinositol 3-Kinases
0302 clinical medicine
microRNA
Humans
RNA, Messenger
Gene
Carcinoma, Renal Cell
lcsh:QH301-705.5
PI3K/AKT/mTOR pathway
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Gene Expression Profiling
TOR Serine-Threonine Kinases
Genomics
Immune checkpoint
Chromatin
Kidney Neoplasms
Gene expression profiling
Survival Rate
MicroRNAs
030104 developmental biology
lcsh:Biology (General)
030220 oncology & carcinogenesis
Mutation
Cancer research
Proto-Oncogene Proteins c-akt
Clear cell
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 14
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....e649156237a85ceb8d4b81c5f0616c94