Extrachromosomal circular DNA landscape of breast cancer with lymph node metastasis

Breast cancer (BC) is a complex disease with diverse manifestations, often resulting in lymph node metastasis (LNM) and impacting patient prognosis. Extrachromosomal circular DNA (eccDNA) has emerged as a key player in tumorigenesis, yet its contribution to BC LNM remains elusive. Here, we examined primary tumors and matched LNM tissues from 19 BC patients using the Circle‐Seq method. We identified a median count of 44,682 eccDNA in primary tumor tissues and 38,057 in their paired LNM tissues. Furthermore, a ladder‐like size distribution is observed in both primary tumor and LNM tissues. Meanwhile, similar repeat sequence distribution and GC content are identified from both primary tissue and LNM tissues. Finally, we found that eccDNA from both groups are flanked with palindromic trinucleotide motifs. These observations indicate that eccDNA of primary tumor and LNM tissues are from similar chromosomal origins. However, a subset of miRNA‐associated eccDNA displayed selective enrichment in metastatic lesions, such as miR‐6730 and miR‐548AA1 genes. This observation implicates the function of miRNA‐related eccDNA in the metastatic cascade. Our study uncovers the potential significance of these unique eccDNA molecules, shedding light on their role in cancer metastasis. What's new? While extrachromosomal circular DNA (eccDNA) has emerged as a key player in tumorigenesis, its contribution to breast cancer lymph node metastases remains elusive. This study shows the presence of distinct eccDNA profiles in primary breast cancers and their corresponding lymph node metastases, highlighting potential new biomarkers for disease progression. The results also demonstrate the differential composition of eccDNA‐embedded microRNA coding genes between primary tumors and lymph node metastases, potentially facilitating the tracking of metastatic breast cancer. These findings have significant implications for the development of targeted therapies and personalized medicine approaches.