alexa 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.
Nephrology

Nephrology

Journal of Kidney

Author(s): Hakimi AA

Abstract Share this page

Purpose: To investigate the impact of newly identified chromosome 3p21 epigenetic tumor suppressors PBRM1, SETD2, and BAP1 on cancer-specific survival (CSS) of 609 patients with clear cell renal cell carcinoma (ccRCC) from 2 distinct cohorts. Experimental Design: Select sequencing on 3p tumor suppressors of 188 patients who underwent resection of primary ccRCC at the Memorial Sloan-Kettering Cancer Center (MSKCC) was conducted to interrogate the genotype–phenotype associations. These findings were compared with analyses of the genomic and clinical dataset from our nonoverlapping The Cancer Genome Atlas (TCGA) cohort of 421 patients with primary ccRCC. Results: 3p21 tumor suppressors are frequently mutated in both the MSKCC (PBRM1, 30.3%; SETD2, 7.4%; BAP1, 6.4%) and the TCGA (PBRM1, 33.5%; SETD2, 11.6%; BAP1, 9.7%) cohorts. BAP1 mutations are associated with worse CSS in both cohorts [MSKCC, P = 0.002; HR 7.71; 95% confidence interval (CI)2.08–28.6; TCGA, P = 0.002; HR 2.21; 95% CI 1.35–3.63]. SETD2 are associated with worse CSS in the TCGA cohort (P = 0.036; HR 1.68; 95% CI 1.04–2.73). On the contrary, PBRM1 mutations, the second most common gene mutations of ccRCC, have no impact on CSS. Conclusion: The chromosome 3p21 locus harbors 3 frequently mutated ccRCC tumor suppressor genes. BAP1 and SETD2 mutations (6%–12%) are associated with worse CSS, suggesting their roles in disease progression. PBRM1 mutations (30%–34%) do not impact CSS, implicating its principal role in the tumor initiation. Future efforts should focus on therapeutic interventions and further clinical, pathologic, and molecular interrogation of this novel class of tumor suppressors. Clin Cancer Res; 19(12); 3259–67. ©2013 AACR. Translational Relevance Several recurrent mutations in 3p chromatin modulators/modifiers (PBRM1, SETD2, and BAP1) have been reported in clear cell renal cell carcinoma (ccRCC) in the past 2 years. We report the association of adverse cancer-specific outcomes with mutations of BAP1 and SETD2 in 2 large, distinct cohorts. Our results point to the need for therapeutic interventions and further clinical, pathologic, and molecular interrogation of this novel class of tumor suppressors, and suggest that they may be used for risk stratification.

This article was published in Clinical Cancer Research and referenced in Journal of Kidney

Relevant Expert PPTs

Relevant Speaker PPTs

  • Laidoudi Aicha
    Acute renal failure and uveitis, which diagnosis is most likely in internal medicine? Tinu syndrome, through two observations
    PPT Version | PDF Version
  • Hisham Hussein Imam
    Pregnancy after renal transplantation
    PPT Version | PDF Version
  • Joachim Struck
    Pro-enkephalin (Penkid): A novel plasma biomarker to assess renal impairment
    PPT Version | PDF Version
  • Dhanya Mohan
    Refractory anemia due to parvovirus b19 infection in a renal transplant recipient
    PPT Version | PDF Version
  • Khalid Bashar
    Predictive parameters of arterio-venous fistula functional maturation in a population of patients with end-stage renal disease
    PPT Version | PDF Version
  • Pearl Pai
    A holistic approach to better manage the renal service and improve patient satisfaction in a new hospital and dialysis centre in China
    PPT Version | PDF Version
  • Bhaskar Reddy
    Persuade of prevention of renal failure in an imperfect world, is it possible in the 21st century?
    PPT Version | PDF Version
  • Ana Laura Pimentel
    Glycated hemoglobin in the screening and diagnosis of renal post-transplantation diabetes
    PPT Version | PDF Version
  • Werner Boecker
    Syringomatous tumour of the nipple and low-grade adenosquamous carcinoma: Evidence for a common origin
    PPT Version | PDF Version
  • Tibor Tot
    Multiparameter characterization of breast carcinoma: subgross, microscopy, proteins, and genes
    PPT Version | PDF Version
  • Fathia El Sharkawi
    The effect of PTEN and TRAIL genes loaded on nanoparticles on hepatocellular carcinoma
    PPT Version | PDF Version
  • Yosef Yarden
    Classically, the 3’untranslated region (3’UTR) is that region in eukaryotic protein-coding genes from the translation termination codon to the polyA signal. It is transcribed as an integral part of the mRNA encoded by the gene. However, there exists another kind of RNA, which consists of the 3’UTR alone, without all other elements in mRNA such as 5’UTR and coding region. The importance of independent 3’UTR RNA (referred as I3’UTR) was prompted by results of artificially introducing such RNA species into malignant mammalian cells. Since 1991, we found that the middle part of the 3’UTR of the human nuclear factor for interleukin-6 (NF-IL6) or C/EBP gene exerted tumor suppression effect in vivo. Our subsequent studies showed that transfection of C/EBP 3’UTR led to down-regulation of several genes favorable for malignancy and to up-regulation of some genes favorable for phenotypic reversion. Also, it was shown that the sequences near the termini of the C/EBP 3’UTR were important for its tumor suppression activity. Then, the C/EBP 3’UTR was found to directly inhibit the phosphorylation activity of protein kinase CPKC in SMMC-7721, a hepatocarcinoma cell line. Recently, an AU-rich region in the C/EBP 3’UTR was found also to be responsible for its tumor suppression. Recently we have also found evidence that the independent C/EBP 3’UTR RNA is actually exists in human tissues, such as fetal liver and heart, pregnant uterus, senescent fibroblasts etc. Through 1990’s to 2000’s, world scientists found several 3’UTR RNAs that functioned as artificial independent RNAs in cancer cells and resulted in tumor suppression. Interestingly, majority of genes for these RNAs have promoter-like structures in their 3’UTR regions, although the existence of their transcribed products as independent 3’UTR RNAs is still to be confirmed. Our studies indicate that the independent 3’UTR RNA is a novel non-coding RNA species whose function should be the regulation not of the expression of their original mRNA, but of some essential life activities of the cell as a whole.
    PPT Version | PDF Version
  • Elena Rampanelli
    Renal dysfunction and metabolic syndrome: the chicken or the egg?
    PPT Version | PDF Version
  • Devathri Nanayakkara
    Context specific role of deubiquitylase enzyme, USP9X in oral squamous cell carcinoma
    PPT Version | PDF Version
  • John D Sullivan
    Creating an oligopoly in the treatment of end stage renal disease and the subsequent impact on home hemodialysis therapies
    PPT Version | PDF Version

Recommended Conferences

  • 11th Global Nephrologists Annual Meeting
    Jun 26-28, 2017, London, UK
  • 2nd Annual Kidney Congress
    Aug 28-30, 2017, Philadelphia, USA
  • 16th European Nephrology Conference
    Oct 02-04, 2017, Barcelona, Spain
  • 16th International Conference on Nephrology
    Nov 02-03, 2017, Atlanta, USA

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

agrifoodaquavet@omicsonline.com

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

clinical_biochem@omicsonline.com

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

business@omicsonline.com

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

chemicaleng_chemistry@omicsonline.com

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

environmentalsci@omicsonline.com

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

engineering@omicsonline.com

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

generalsci_healthcare@omicsonline.com

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

genetics_molbio@omicsonline.com

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

immuno_microbio@omicsonline.com

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

omics@omicsonline.com

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

materialsci@omicsonline.com

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

mathematics_physics@omicsonline.com

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

medical@omicsonline.com

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

neuro_psychology@omicsonline.com

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

pharma@omicsonline.com

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

social_politicalsci@omicsonline.com

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version