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Abstract Pathogenic BRCA1 and BRCA2 germline variants confer an increased risk of hereditary breast and ovarian cancer (HBOC). In this high-risk cohort, novel biomarkers are needed to support patient management. While circulating cell-free DNA-based conventional CpG-level averaging is promising, it dilutes tumor-specific signals in samples with low circulating tumor DNA (ctDNA) fractions.
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