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.

中文翻译：

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乳腺癌淋巴结转移的染色体外环状DNA图谱

乳腺癌（BC）是一种表现多样的复杂疾病，常导致淋巴结转移（LNM）并影响患者预后。染色体外环状 DNA (eccDNA) 已成为肿瘤发生的关键因素，但其对 BC LNM 的贡献仍然难以捉摸。在这里，我们使用 Circle‐Seq 方法检查了 19 名 BC 患者的原发肿瘤和匹配的 LNM 组织。我们在原发性肿瘤组织中确定了 eccDNA 的中位数为 44,682 个，在其配对的 LNM 组织中确定了 38,057 个 eccDNA。此外，在原发肿瘤和 LNM 组织中均观察到阶梯状大小分布。同时，在原代组织和 LNM 组织中发现了相似的重复序列分布和 GC 含量。最后，我们发现两组的 eccDNA 两侧都有回文三核苷酸基序。这些观察结果表明原发肿瘤和 LNM 组织的 eccDNA 具有相似的染色体起源。然而，miRNA 相关 eccDNA 的一个子集在转移性病变中表现出选择性富集，例如miR-6730和miR-548AA1基因。这一观察结果暗示了 miRNA 相关 eccDNA 在转移级联中的功能。我们的研究揭示了这些独特的 eccDNA 分子的潜在意义，揭示了它们在癌症转移中的作用。