Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer
Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer
复制标题
DOI：
10.1016/j.celrep.2016.06.051
复制
发表时间：
2016-07-26
期刊：
影响因子：
8.8
通讯作者：
Sorlie, Therese
中科院分区：
文献类型：
--
作者：
Lesurf, Robert;Aure, Miriam Ragle;Sorlie, Therese
乳腺癌由至少五种主要的分子“内在”亚型组成，反映在侵袭前和侵袭性疾病中。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经确立，但目前尚不清楚是什么机制驱动了进展，以及进展机制是依赖于还是独立于亚型。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拷贝数谱，以便全面鉴定参与乳腺癌进展的基因、信号通路、过程和细胞类型。我们的工作提供了证据，表明存在与内在亚型特有的疾病进展相关的分子特征。此外，我们还建立了亚型特异性特征，能够识别一小部分表达谱与浸润性癌相似的侵袭前肿瘤，表明未来疾病进展的可能性更高。
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.