High-Resolution Bisulfite-Sequencing of Peripheral Blood DNA Methylation in Early-Onset and Familial Risk Breast Cancer Patients
Autor: | James M. Ford, Joshua J. Gruber, Natalie Jäger, Maria K. Haanpää, Justin Chen, Michael Snyder |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Adult Epigenomics Cancer Research Bisulfite sequencing Breast Neoplasms Proto-Oncogene Mas Article 03 medical and health sciences Young Adult 0302 clinical medicine Breast cancer Neoplastic Syndromes Hereditary Biomarkers Tumor Medicine Humans Sulfites Genetic Predisposition to Disease Epigenetics Allele skin and connective tissue diseases Promoter Regions Genetic BRCA2 Protein business.industry BRCA1 Protein PTEN Phosphohydrolase Cancer Methylation DNA Methylation Middle Aged medicine.disease 030104 developmental biology Oncology 030220 oncology & carcinogenesis Case-Control Studies DNA methylation Cancer research CpG Islands Female business Ovarian cancer Transcription Factors |
Popis: | Purpose: Understanding and explaining hereditary predisposition to cancer has focused on the genetic etiology of the disease. However, mutations in known genes associated with breast cancer, such as BRCA1 and BRCA2, account for less than 25% of familial cases of breast cancer. Recently, specific epigenetic modifications at BRCA1 have been shown to promote hereditary breast cancer, but the broader potential for epigenetic contribution to hereditary breast cancer is not yet well understood. Experimental Design: We examined DNA methylation through deep bisulfite sequencing of CpG islands and known promoter or regulatory regions in peripheral blood DNA from 99 patients with familial or early-onset breast or ovarian cancer, 6 unaffected BRCA mutation carriers, and 49 unaffected controls. Results: In 9% of patients, we observed altered methylation in the promoter regions of genes known to be involved in cancer, including hypermethylation at the tumor suppressor PTEN and hypomethylation at the proto-oncogene TEX14. These alterations occur in the form of allelic methylation that span up to hundreds of base pairs in length. Conclusions: Our observations suggest a broader role for DNA methylation in early-onset, familial risk breast cancer. Further studies are warranted to clarify these mechanisms and the benefits of DNA methylation screening for early risk prediction of familial cancers. |
Databáze: | OpenAIRE |
Externí odkaz: |