Research Paper Volume 13, Issue 8 pp 11860—11876

Genetic landscape of breast cancer and mutation tracking with circulating tumor DNA in Chinese women

Yinghao Wang1, *, , Lizhi Lin1, *, , Linhong Li2, *, , Jialiang Wen1, , Yili Chi1, , Rutian Hao1, , Xuanxuan Dai1, , Yizuo Chen1, , Duping Huang1, , Yili Zhou1, , Jie You1, , Zhiqiang Ye1, , Hao Chen1, , Lingli Jin1, , Danxiang Chen1, , Fan Yang1, , Erjie Xia1, , Xueyan Ma2, , Fengyu Guo2, , Yunguang Tong2, , Min Zheng3, &, , Ouchen Wang1, ,

  • 1 Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, P.R. China
  • 2 Omigen, Inc., Hangzhou 310000, P.R. China
  • 3 Department of Breast Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, P.R. China
* Equal contribution

Received: January 28, 2021       Accepted: March 6, 2021       Published: April 23, 2021
How to Cite

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Considerable efforts have been devoted to exploring the breast cancer mutational landscape to understand its genetic complexity. However, no studies have yet comprehensively elucidated the molecular characterization of breast tumors in Chinese women. This study aimed to determine the potential clinical utility of peripheral blood assessment for circulating tumor-derived DNA (ctDNA) and comprehensively characterize the female Chinese population’s genetic mutational spectrum. We used Omi-Seq to create cancer profiles of 273 patients enrolled at The First Affiliated Hospital of Wenzhou Medical University. The gene landscape results indicate PIK3CA and TP53 as the most frequently detected genes, followed by ERBB2, in Chinese breast cancer patients. The accuracy of ERBB2 copy number variations in tissue/formalin-fixed and paraffin-embedded samples was 95% with 86% sensitivity and 99% specificity. Moreover, mutation numbers varied between different molecular cell-free DNA subtypes, with the basal-like patients harboring a higher number of variants than the luminal patients. Furthermore, ratio changes in the max ctDNA allele fraction highly correlated with clinical response measurements, including cancer relapse and metastasis. Our data demonstrate that ctDNA characterization using the Omi-Seq platform can extend the capacity of personalized clinical cancer management.


ctDNA: circulating tumor-derived DNA; HER2: human epidermal growth factor receptor 2; NGS: next-generation sequencing; SMI: single molecular identifier; DMIs: digital molecular identifiers; AI: aromatase inhibitor; PARP: poly ADP ribose polymerase; cfDNA: cell-free DNA; AF: allele fraction; ctF: the highest cfDNA allele frequency; TMBs: tumor mutational burdens; IHC: Immunohistochemistry; FISH: Fluorescence in situ hybridization; TNBC: triple-negative breast cancer; HRD: homologous recombination deficiency; TNM: tumor, node, and metastasis; WBC: white blood cells; FFPE: formalin-fixed and paraffin-embedded; PCR: polymerase chain reaction; QC: quality control; SNV: single-nucleotide variant; CNV: copy number variation; LOH: loss of heterozygosity; TAI: telomere allelic imbalance; LST: large-scale state transition.