Whole‐genome circulating tumor DNA methylation landscape reveals sensitive biomarkers of breast cancer. Issue 3 (17th June 2022)

• Record Type: Journal Article
• Authors: Hai, Luo; Li, Lingyu; Liu, Zongzhi; Tong, Zhongsheng; Sun, Yingli
• Is Part Of: MedComm. Volume 3:Issue 3(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-17
• Subjects: biomarkers -- breast cancer -- circulating tumor DNA -- early detection; 610
• DOI: 10.1002/mco2.134
• Languages: English
• ISSNs: 2688-2663

Abstract

Abstract: The changes in circulating tumor DNA (ctDNA) methylation are believed to be early events in breast cancer initiation, which makes them suitable as promising biomarkers for early diagnosis. However, applying ctDNA in breast cancer early diagnosis remains highly challenging due to the contamination of background DNA from blood and low DNA methylation signals. Here, we report an improved way to extract ctDNA, reduce background contamination, and build a whole‐genome bisulfite sequencing (WGBS) library from different stages of breast cancer. We first compared the DNA methylation data of 74 breast cancer patients with those of seven normal controls to screen candidate methylation CpG site biomarkers for breast cancer diagnosis. The obtained 26 candidate ctDNA methylation biomarkers produced high accuracy in breast cancer patients (area under the curve [AUC] = 0.889; sensitivity: 100%; specificity: 75%). Furthermore, we revealed potential ctDNA methylated CpG sites for detecting early‐stage breast cancer (AUC = 0.783; sensitivity: 93.44%; specificity: 50%). In addition, different subtypes of breast cancer could be well distinguished by the ctDNA methylome, which was obtained through our improved ctDNA‐WGBS method. Overall, we identified high specificity and sensitivity breast cancer‐specific methylation CpG site biomarkers, and they will be expected to have the potential to be translated to clinical practice. Abstract : This study demonstrates the utility of circulating tumor DNA (ctDNA) methylation analysis in early detection and molecular subtyping for breast cancer. The improved ctDNA whole‐genome bisulfite sequencing method was effective at developing novel sensitive and specific biomarkers for the diagnosis, early detection, and molecular subtyping of breast cancer. We anticipate that the method and diagnostic biomarkers of breast cancer have substantial clinical translation potential.