IRIBHM, Université Libre de Bruxelles (ULB), 808 route de Lennik, Brussels, 1070, Belgium.
J.-C. Heuson Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Bld de Waterloo, 125, Brussels, 1000, Belgium.
Genes Chromosomes Cancer. 2018 Jul;57(7):331-338. doi: 10.1002/gcc.22533. Epub 2018 Mar 22.
The advent of next generation sequencing technologies has boosted the interest in exploring the role of fusion genes in the development and progression of solid tumors. In breast cancer, most of the detected gene fusions seem to be "passenger" events while the presence of recurrent and driver fusions is still under study. We performed RNA sequencing in 55 well-characterized breast cancer samples and 10 adjacent normal breast tissues, complemented by an analysis of SNP array data. We explored the presence of fusion genes and defined their association with breast cancer subtypes, clinical-pathologic characteristics and copy number aberrations. Overall, 370 fusions were detected across the majority of the samples. HER2+ samples had significantly more fusions than triple negative and luminal subtypes. The number of fusions was correlated with histological grade, Ki67 and tumor size. Clusters of fusion genes were observed across the genome and a significant correlation of fusions with copy number aberrations and more specifically amplifications was also revealed. Despite the large number of fusion events, only a few were recurrent, while recurrent individual genes forming fusions with different partners were also detected including the estrogen receptor 1 gene in the previously detected ESR1-CCDC170 fusion. Overall we detected novel gene fusion events while we confirmed previously reported fusions. Genomic hotspots of fusion genes, differences between subtypes and small number of recurrent fusions are the most relevant characteristics of these events in breast cancer. Further investigation is necessary to comprehend the biological significance of these fusions.
下一代测序技术的出现推动了人们探索融合基因在实体瘤发生和发展中的作用。在乳腺癌中，大多数检测到的基因融合似乎是“乘客”事件，而反复出现和驱动融合的存在仍在研究中。我们对 55 个特征明确的乳腺癌样本和 10 个相邻的正常乳腺组织进行了 RNA 测序，并辅以 SNP 阵列数据分析。我们探索了融合基因的存在，并定义了它们与乳腺癌亚型、临床病理特征和拷贝数异常的关系。总的来说，大多数样本中都检测到了 370 个融合。HER2+样本的融合数量明显多于三阴性和 luminal 亚型。融合的数量与组织学分级、Ki67 和肿瘤大小相关。融合基因簇在整个基因组中观察到，并且还揭示了融合与拷贝数异常的显著相关性，特别是与扩增的相关性。尽管融合事件数量众多，但只有少数是反复出现的，而反复出现的个别基因与不同的伙伴形成融合也被检测到，包括先前检测到的 ESR1-CCDC170 融合中的雌激素受体 1 基因。总的来说，我们检测到了新的基因融合事件，同时也证实了以前报道的融合。融合基因的基因组热点、亚型之间的差异和少数反复出现的融合是这些乳腺癌融合事件的最相关特征。需要进一步的研究来理解这些融合的生物学意义。
