The vast array of cell states found across human tissue arises from chromatin variants, which correspond to segments of the genome, known as DNA elements, adopting a different chromatin state over cell state transitions. Oncogenesis stems from alterations to the chromatin states over DNA elements that result in cancer-associated chromatin variants. Here, we review how cancer-associated chromatin variants call attention to repetitive DNA elements, and guide the functional characterization of transposable elements to decode their role in oncogenesis. We further discuss prevailing opportunities in the study of repetitive DNA elements to move towards the 'complete cancer genome' goal for precision medicine in oncology.
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http://dx.doi.org/10.1016/j.gde.2022.101911 | DOI Listing |
Trends Genet
January 2025
Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mental Illness Research Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, NY 10468, USA; Center for Precision Medicine and Translational Therapeutics, James J. Peters VA Medical Center, Bronx, NY 10468, USA. Electronic address:
Neuropsychiatric and neurodegenerative diseases have a significant genetic component. Risk variants often affect the noncoding genome, altering cis-regulatory elements (CREs) and chromatin structure, ultimately impacting gene expression. Chromatin accessibility profiling methods, especially assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), have been used to pinpoint disease-associated SNPs and link them to affected genes and cell types in the brain.
View Article and Find Full Text PDFJ Pathol
January 2025
SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), Institut Curie, Université Paris Cité, Paris, France.
Rhabdoid tumours (RT) are an aggressive malignancy affecting <2-year-old infants, characterised by biallelic loss-of-function alterations in SWI/SNF-related BAF chromatin remodelling complex subunit B1 (SMARCB1) in nearly all cases. Germline SMARCB1 alterations are found in ~30% of patients and define the RT Predisposition Syndrome type 1 (RTPS1). Uveal melanoma (UVM), the most common primary intraocular cancer in adults, does not harbour SMARCB1 alterations.
View Article and Find Full Text PDFInt J Cancer
January 2025
Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Prostate cancer is a common malignancy that in 5%-30% leads to treatment-resistant and highly aggressive disease. Metastasis-potential and treatment-resistance is thought to rely on increased plasticity of the cancer cells-a mechanism whereby cancer cells alter their identity to adapt to changing environments or therapeutic pressures to create cellular heterogeneity. To understand the molecular basis of this plasticity, genomic studies have uncovered genetic variants to capture clonal heterogeneity of primary tumors and metastases.
View Article and Find Full Text PDFLife Sci Alliance
April 2025
National Cancer Institute, Center for Cancer Research, Laboratory of Receptor Biology and Gene Expression, Bethesda, MD, USA
Centromeres are marked by the centromere-specific histone H3 variant CENP-A/CENH3. Throughout the cell cycle, the constitutive centromere-associated network is bound to CENP-A chromatin, but how this protein network modifies CENP-A nucleosome conformations in vivo is unknown. Here, we purify endogenous centromeric chromatin associated with the CENP-C complex across the cell cycle and analyze the structures by single-molecule imaging and biochemical assays.
View Article and Find Full Text PDFCell
January 2025
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:
A meta-genome-wide association study across eight psychiatric disorders has highlighted the genetic architecture of pleiotropy in major psychiatric disorders. However, mechanisms underlying pleiotropic effects of the associated variants remain to be explored. We conducted a massively parallel reporter assay to decode the regulatory logic of variants with pleiotropic and disorder-specific effects.
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