Recent sequencing studies of clear cell (conventional) renal cell carcinoma (ccRCC) have identified inactivating point mutations in the chromatin-modifying genes PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2 and BAP1. To investigate whether aberrant hypermethylation is a mechanism of inactivation of these tumor suppressor genes in ccRCC, we sequenced the promoter region within a bona fide CpG island of PBRM1, KDM6A, SETD2 and BAP1 in bisulfite-modified DNA of a representative series of 50 primary ccRCC, 4 normal renal parenchyma specimens and 5 RCC cell lines. We also interrogated the promoter methylation status of KDM5C and ARID1A in the Cancer Genome Atlas (TCGA) ccRCC Infinium data set. PBRM1, KDM6A, SETD2 and BAP1 were unmethylated in all tumor and normal specimens. KDM5C and ARID1A were unmethylated in the TCGA 219 ccRCC and 119 adjacent normal specimens. Aberrant promoter hypermethylation of PBRM1, BAP1 and the other chromatin-modifying genes examined here is therefore absent or rare in ccRCC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741218 | PMC |
| http://dx.doi.org/10.4161/epi.24552 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Epigenetics in Neurodegenerative Diseases.
Subcell Biochem
January 2025
Faculty of Medicine and Faculty of Life Sciences, Institute of Biomedical Sciences (ICB), Universidad Andres Bello, Santiago, Chile.
Healthy brain functioning requires a continuous fine-tuning of gene expression, involving changes in the epigenetic landscape and 3D chromatin organization. Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are three multifactorial neurodegenerative diseases (NDDs) that are partially explained by genetics (gene mutations and genetic risk factors) and influenced by non-genetic factors (i.e.
View Article and Find Full Text PDFMetabolism-epigenetic interaction-based bone and dental regeneration: From impacts and mechanisms to treatment potential.
Bone
December 2024
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Centre for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Centre of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China. Electronic address:
Article Synopsis
- Metabolic pathways in bone and dental loss show regulated changes in activity, indicating metabolic plasticity that is energy-intensive.
- These changes are linked to epigenetic modifications that affect how enzymes involved in metabolism operate, thereby influencing cellular functions.
- The review focuses on the relationship between metabolic reprogramming and epigenetic modifications in bone and dental cells, exploring implications for treatment and highlighting inconsistencies in current research.
Identification of Potential Genes in Rheumatoid Arthritis-Associated Interstitial Lung Disease Using RNA-seq and In Vitro Analyses.
Cell Biochem Funct
January 2025
Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an increasingly recognized extra-articular manifestations (EAMs) in the RA, with highly morbidity and mortality. The identification of key molecules involved in RA-ILD has a high requirement in clinic, and the role of their transcriptional regulation in the etiology of RA-ILD is great significant for investigation. In this study, we collected the whole peripheral blood samples of RA-ILD and RA only patients to bulk RNA-sequence.
View Article and Find Full Text PDFTargeting chromatin modifying complexes in acute myeloid leukemia.
Stem Cells Transl Med
November 2024
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
Article Synopsis
- Acute myeloid leukemia (AML) is a serious blood cancer characterized by frequent relapses, partly due to disruptions in chromatin modifications that affect cell behavior.
- Aberrant histone modifications lead to the activation of self-renewal genes in specific hematopoietic progenitor cells, which are crucial for the development of AML, particularly in cases with MLL rearrangements and NPM1 mutations.
- New research highlights how leukemic cells exploit histone modification complexes as potential treatment targets, and the review suggests combining therapies that inhibit these complexes to improve effectiveness and tackle resistance to current treatments.
Loss of SETD2 in wild-type VHL clear cell renal cell carcinoma sensitizes cells to STF-62247 and leads to DNA damage, cell cycle arrest, and cell death characteristic of pyroptosis.
Mol Oncol
November 2024
Department of Chemistry and Biochemistry, Université de Moncton, Canada.
Loss of chromosome 3p and loss of heterogeneity of the von Hippel-Lindau (VHL) gene are common characteristics of clear cell renal cell carcinoma (ccRCC). Despite frequent mutations on VHL, a fraction of tumors still grows with the expression of wild-type (WT) VHL and evolve into an aggressive subtype. Additionally, mutations on chromatin-modifying genes, such as the gene coding for the histone methyltransferase SET containing domain 2 (SETD2), are essential to ccRCC evolution.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!