Creating a ‘Timeline’ of ductal carcinoma in situ to identify processes and biomarkers for progression towards invasive ductal carcinoma
Clare A. Rebbeck,Jian Xian,Susanne Bornelöv,Joseph Geradts,Amy Hobeika,Heather Geiger,Jose Franco Alvarez,Elena Rozhkova,Ashley Nicholls,Nicolas Robine,H. Kim Lyerly,Gregory J. Hannon +11 more
TLDR
A ‘Timeline’ of disease progression is generated, utilising the variability within patients and combining >2,000 individually micro-dissected ductal lesions from 145 patients into one continuous trajectory, showing there is a progressive loss in basal layer integrity, coupled with two epithelial to mesenchymal transitions (EMT) early in the timeline.Abstract:
Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive disease is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients and even within patients. Using gene expression analysis, we have generated a ‘Timeline’ of disease progression, utilising the variability within patients and combining >2,000 individually micro-dissected ductal lesions from 145 patients into one continuous trajectory. Using this Timeline we show there is a progressive loss in basal layer integrity, coupled with two epithelial to mesenchymal transitions (EMT), one early in the timeline and a second just prior to cells leaving the duct. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.read more
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Alexander Dobin,Carrie A. Davis,Felix Schlesinger,Jorg Drenkow,Chris Zaleski,Sonali Jha,Philippe Batut,Mark Chaisson,Thomas R. Gingeras +8 more
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voom: precision weights unlock linear model analysis tools for RNA-seq read counts
Charity W. Law,Charity W. Law,Yunshun Chen,Yunshun Chen,Wei Shi,Wei Shi,Gordon K. Smyth,Gordon K. Smyth +7 more
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