Single CpG hypermethylation, allele methylation errors, and decreased expression of multiple tumor suppressor genes in normal body cells of mutation‐negative early‐onset and high‐risk breast cancer patients
| Autor: | Larissa Haertle, Christian Sutter, Silke Appenzeller, Tamara Schneider, Thomas Haaf, Julia Böck, Andrea Gehrig, J. Schröder, Beat Wolf, Simone Rost, Claus R. Bartram |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Cancer Research Tumor suppressor gene Bisulfite sequencing early onset breast cancer Breast Neoplasms Biology Cancer Genetics and Epigenetics Epigenesis Genetic 03 medical and health sciences breast cancer susceptibility gene Risk Factors Biomarkers Tumor Humans allele methylation error Genetic Predisposition to Disease Epigenetics Breast Allele tumor suppressor gene Promoter Regions Genetic Alleles epimutation familial breast cancer Tumor Suppressor Proteins deep bisulfite sequencing Methylation DNA Methylation Prognosis Gene Expression Regulation Neoplastic 030104 developmental biology Oncology CpG site Tumor progression Case-Control Studies DNA methylation Mutation Cancer research CpG Islands Female single CpG hypermethylation |
| Zdroj: | International Journal of Cancer |
| ISSN: | 1097-0215 0020-7136 |
| Popis: | To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2‐mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression. We analyzed blood samples of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a heterozygous mutation, respectively, along with age‐matched controls. Methylation analysis of up to 50,000 individual DNA molecules per gene and sample allowed quantification of epimutations (alleles with >50% methylated CpGs), which are associated with epigenetic silencing. Compared to ESR1, which is representative for an average promoter, TS genes were characterized by a very low (< 1%) average methylation level and a very low mean epimutation rate (EMR What's new? Cancer can change patterns of DNA methylation, with widespread loss of methylation but also localized increases in methylation. Here, the authors analyzed blood cells, looking for differences in methylation between breast cancer patients and healthy persons. They developed a deep bisulfite sequencing assay to specifically test the promoter regions of 8 tumor suppressor genes, plus the estrogen receptor gene, along with reduced tumor suppressor gene expression. They found that breast cancer patients showed increased methylation changes in multiple tumor suppressor genes, reduced tumor suppressor gene expression. Thus, epigenetic abnormalities could indicate disruptions in the mechanisms that maintain proper methylation, and could signal increased tumor risk. |
| Databáze: | OpenAIRE |
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