Lesurf Robert, Aure Miriam Ragle, Mørk Hanne Håberg, Vitelli Valeria, Lundgren Steinar, Børresen-Dale Anne-Lise, Kristensen Vessela, Wärnberg Fredrik, Hallett Michael, Sørlie Therese
Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada; McGill Centre for Bioinformatics, McGill University, Montreal, QC H3G 1Y6, Canada; Rosalind & Morris Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Institute for Cancer Research and Department of Cancer Genetics, Oslo University Hospital, The Norwegian Radium Hospital, 0424 Oslo, Norway; K.G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, 0318 Oslo, Norway.
Cell Rep. 2016 Jul 26;16(4):1166-1179. doi: 10.1016/j.celrep.2016.06.051. Epub 2016 Jul 7.
Breast cancer consists of at least five main molecular "intrinsic" subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.
乳腺癌至少由五种主要的分子“内在”亚型组成，这些亚型在癌前病变和浸润性疾病中均有体现。尽管先前的研究表明浸润性乳腺癌的许多分子特征在早期就已确立，但尚不清楚驱动进展的机制是什么，以及进展机制是否依赖于亚型或与亚型无关。我们从总共59例原位病变和85例浸润性肿瘤中生成了mRNA、miRNA和DNA拷贝数图谱，以便全面识别参与乳腺癌进展的那些基因、信号通路、过程和细胞类型。我们的研究提供了证据，表明存在与疾病进展相关的分子特征，这些特征是内在亚型所特有的。我们还建立了亚型特异性特征，能够识别一小部分具有类似于浸润性癌表达谱的癌前肿瘤，这表明未来疾病进展的可能性更高。
