The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

SUMMARY Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival.

• Publication year

  2018

• Venue

  Cell Reports

• Publication date

  2018-04-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.celrep.2018.03.075PMID 38578829PMCID 6075733
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma.

  2018cited by this paper
• Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276)

  2017cited by this paper
• Genomic landscape and evolution of metastatic chromophobe renal cell carcinoma.

  2017cited by this paper
• Mitochondrial respiratory gene expression is suppressed in many cancers

  2017cited by this paper
• Targeting CDK4/6 in patients with cancer.

  2016cited by this paper
• The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

  2016cited by this paper
• MuSE: accounting for tumor heterogeneity using a sample-specific error model improves sensitivity and specificity in mutation calling from sequencing data

  2016influential reference
• Immune Checkpoint Therapy in Renal Cell Carcinoma

  2016cited by this paper
• Avoiding common pitfalls when clustering biological data

  2016cited by this paper
• Claudin-low bladder tumors are immune infiltrated and actively immune suppressed.

  2016cited by this paper
• Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures

  2016cited by this paper
• Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma.

  2016influential reference
• Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

  2016cited by this paper
• Dynamic reprogramming of DNA methylation in SETD2-deregulated renal cell carcinoma

  2015cited by this paper
• Biological determinants of bladder cancer gene expression subtypes

  2015cited by this paper
• Large-scale profiling of microRNAs for The Cancer Genome Atlas

  2015cited by this paper
• Alternative preprocessing of RNA-Sequencing data in The Cancer Genome Atlas leads to improved analysis results

  2015cited by this paper
• Immune signature of tumor infiltrating immune cells in renal cancer

  2015influential reference
• Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.

  2015cited by this paper
• Mitochondrial DNA copy number variation across human cancers

  2015cited by this paper
• MToolBox: a highly automated pipeline for heteroplasmy annotation and prioritization analysis of human mitochondrial variants in high-throughput sequencing

  2014influential reference
• Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

  2014cited by this paper
• Prognostic B-cell Signatures Using mRNA-Seq in Patients with Subtype-Specific Breast and Ovarian Cancer

  2014cited by this paper
• Targeting ABL1-mediated oxidative stress adaptation in fumarate hydratase-deficient cancer.

  2014cited by this paper
• The somatic genomic landscape of chromophobe renal cell carcinoma.

  2014cited by this paper
• Tumor-Specific Hypermethylation of Epigenetic Biomarkers, Including SFRP1, Predicts for Poorer Survival in Patients from the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) Project

  2014cited by this paper
• The pentose phosphate pathway and cancer.

  2014cited by this paper
• RADIA: RNA and DNA Integrated Analysis for Somatic Mutation Detection

  2014influential reference
• The genetic basis of kidney cancer

  2014cited by this paper
• STAR: ultrafast universal RNA-seq aligner

  2013influential reference
• MiTCR: software for T-cell receptor sequencing data analysis

  2013influential reference
• Author Manuscript

  2013cited by this paper
• Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples

  2013influential reference
• Adverse Outcomes in Clear Cell Renal Cell Carcinoma with Mutations of 3p21 Epigenetic Regulators BAP1 and SETD2: A Report by MSKCC and the KIRC TCGA Research Network

  2013cited by this paper
• COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

  2013cited by this paper
• Finding consistent patterns: A nonparametric approach for identifying differential expression in RNA-Seq data

  2013influential reference
• Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation.

  2013cited by this paper
• Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.

  2013cited by this paper
• Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics

  2012cited by this paper
• VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing.

  2012influential reference
• Differential analysis of gene regulation at transcript resolution with RNA-seq

  2012influential reference
• SomaticSniper: identification of somatic point mutations in whole genome sequencing data

  2012influential reference
• Building prognostic models for breast cancer patients using clinical variables and hundreds of gene expression signatures

  2011cited by this paper
• Wnt antagonist DKK1 acts as a tumor suppressor gene that induces apoptosis and inhibits proliferation in human renal cell carcinoma

  2011cited by this paper
• An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma.

  2011cited by this paper
• The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.

  2010cited by this paper
• ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking

  2010influential reference
• The genetic basis of kidney cancer: a metabolic disease

  2010cited by this paper
• A clinically relevant gene signature in triple negative and basal-like breast cancer

  2010cited by this paper
• Allele-specific copy number analysis of tumors

  2010influential reference
• The Macrophage Colony-Stimulating Factor 1 Response Signature in Breast Carcinoma

  2009cited by this paper
• T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers

  2009cited by this paper
• The Sequence Alignment/Map format and SAMtools

  2009influential reference
• Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads

  2009influential reference
• Integrated detection and population-genetic analysis of SNPs and copy number variation

  2008influential reference
• The humoral immune system has a key prognostic impact in node-negative breast cancer.

  2008cited by this paper
• An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer

  2007cited by this paper
• Wnt Antagonist Family Genes as Biomarkers for Diagnosis, Staging, and Prognosis of Renal Cell Carcinoma Using Tumor and Serum DNA

  2006cited by this paper
• Cell-type specific gene expression profiles of leukocytes in human peripheral blood

  2006cited by this paper
• GMAP: a genomic mapping and alignment program for mRNA and EST sequence

  2005influential reference
• MUSCLE: a multiple sequence alignment method with reduced time and space complexity

  2004influential reference
• Consensus Clustering: A Resampling-Based Method for Class Discovery and Visualization of Gene Expression Microarray Data

  2003cited by this paper
• Renal cell carcinoma.

  1956cited by this paper

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• Prevailing challenges in personalized treatment for metastatic renal cell carcinoma: a narrative review

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