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Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma
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Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma
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Journal Article
Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma
2022
Overview
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 ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. 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.
Progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) remains poorly understood. Here, the authors analyse over 2700 micro-dissected samples using transcriptomics to identify genes that characterise different stages of DCIS to IDC progression, and identify IDC-associated markers within early-stage lesions.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Biomarkers, Tumor - genetics
/ Breast Neoplasms - pathology
/ Carcinoma, Ductal, Breast - metabolism
/ Carcinoma, Intraductal, Noninfiltrating - genetics
/ Carcinoma, Intraductal, Noninfiltrating - pathology
/ Female
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Lesions
/ Science
