American Association for Cancer Research
10780432ccr182423-sup-206005_3_supp_5556672_psbx24.pdf (906.75 kB)

Supplementary Figure S4 from High-Resolution Bisulfite-Sequencing of Peripheral Blood DNA Methylation in Early-Onset and Familial Risk Breast Cancer Patients

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journal contribution
posted on 2023-03-31, 20:48 authored by Justin Chen, Maria K. Haanpää, Joshua J. Gruber, Natalie Jäger, James M. Ford, Michael P. Snyder

Figure S4. Individual CpG methylation ratios at genes with promoters identified to have statistically significant differences in methylation. Low coverage at the ends of target enrichment regions lead to noise that artificially affects average methylation at ABRAXAS1 (A), MSH2 (B), STK11 (C), and TP53 (D). The gene structures are displayed below the heatmaps at their appropriate locations. Thin grey rectangles indicate the UTRs and thick blue rectangles indicate CDS; introns are represented by dashed lines. Arrows indicate putative TSS starts and the direction of transcription.






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. 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. 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. 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.