乳腺癌是女性最常见的严重威胁女性健康的恶性肿瘤,发病机制至今仍不是很明确，亟待挖掘。融合基因在血液恶性肿瘤和软组织肉瘤中有关发病机制的广泛研究提示融合基因是癌症的致病机制之一，是肿瘤发展的一个重要原因。但对于很常见的实体瘤，融合基因的致病作用却未得到充分重视。通过新一代测序技术(Next-Generation Sequencing)进行末端配对RNA测序(Paired-end RNA-seq)，我们发现2个乳腺癌特异性且高表达（普遍性均达到68%）的融合基因LOC100134368 －NME4和SF3A2-AMH，这一发现提示这两个融合基因可能与乳腺癌关系密切，因此本研究将进一步开展这两个融合基因表达的临床意义及预后价值，与乳腺癌发生发展的关系、功能和作用机制的深入系统研究，有望对揭示乳腺癌的发生发展的分子机制，提供诊断、预后判断的标志物和干预治疗的分子靶点提供新线索。

Breast cancer is the most common malignancy in women and is a serious threat to women's health. The pathogenesis is still not very clear, so urgent mining is needed. The extensive studies on fusion genes and their pathogenetic mechanism in hematological malignancies and soft-tissue sarcoma suggested that gene fusion is a major cause in cancer development. However, the oncogenesis role of fusion genes in solid tumors was largely underappreciated. Using paired-end RNA sequencing by next-generation sequencing technology, we found two fusion genes, LOC100134368-NME4 and SF3A2-AMH, specifically expressed in breasr cancer and with high prevalence(68%). This finding suggests that the two fusion genes may be closely related to the initiation and development of breast cancer. In this study we will further evaluate the clinical significance and prognostic value of the fusion genes and explore their functions and the underlying mechanisms in breast cancer development. The systematic study of the two fusion genes may reveal the molecular mechanisms of breast cancer development and provide prognostic markers and new molecular targets for therapy.

通过新一代测序技术(Next-Generation Sequencing)进行末端配对RNA测序(Paired-end RNA-seq)，我们发现2个乳腺癌特异性的融合基因LOC100134368 －NME4和SF3A2-AMH，我们收集了38对中国乳腺癌肿瘤组织和正常组织，并收集了38例患者的临床信息，通过RT-PCR方法进行扩增，发现2个融合基因SF3A2-AMH和LOC100134368 －NME4主要在肿瘤中表达，表达比例分别为55％（21/38）和63％（24/38），在对应的正常组织中表达较低，分别为13％（5/38）和16％（6/38）。对乳腺癌患者肿瘤组织中SF3A2-AMH和LOC100134368–NME4的检出与乳腺癌的分子分型之间（Luminal A型, Luminal B型,Her2过表达型，基底细胞型）的相关性进行了分析，结果显示不同分子分型之间融合基因的表达率并无显著差异。在乳腺癌患者外周血血浆循环核酸中进行乳腺癌特异融合基因SF3A2-AMH和LOC100134368–NME4的检测，应用QIAamp Circulating Nucleic Acid Kit从血浆中纯化并浓缩游离RNA，经RT-PCR进行检测，未发现两种融合基因的表达。此研究提示这两个融合基因可能与乳腺癌关系密切，因此我们将进一步开展这两个融合基因表达的功能和作用机制的深入系统研究。