Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Bld de Waterloo 121, 1000 Brussels, Belgium.
Laboratory of Translational Genetics, Vesalius Research Center, VIB, Campus Gasthuisberg, O&N IV Herestraat 49, 3000 Leuven, Belgium.
Nat Commun. 2017 Apr 20;8:14944. doi: 10.1038/ncomms14944.
Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common 'metastatic precursor'. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination.
使用全外显子测序和拷贝数分析对十名尸检患者的原发和多个匹配转移瘤进行分析后，我们利用系统发生技术推断了乳腺癌进展的进化史。我们观察到两种疾病进展模式。在一些患者中，所有远处转移灶都聚集在与其原发灶分开的分支上。体细胞突变的克隆频率分析表明，转移灶具有单克隆起源，来自一个共同的“转移前体”。或者，多个转移病灶是由原发肿瘤内的不同克隆播种而来。我们进一步表明转移灶可以水平交叉播种。这些发现为乳腺癌的扩散提供了新的认识。
