Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma

Nature Communications
Moustafa AbdallaSusan J Done

Abstract

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development.

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Citations

Sep 27, 2018·Frontiers in Oncology·Jean-Pascal Capp, Régis Bataille
Jan 9, 2019·Frontiers in Genetics·Manuela SollazzoDaniela Grifoni
Sep 19, 2019·Evolution, Medicine, and Public Health·Mathieu GiraudeauFrédéric Thomas
Jun 16, 2018·Scientific Reports·Xuezheng SunMelissa A Troester
Oct 30, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jean-Pascal Capp, Frédéric Thomas

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Datasets Mentioned

BETA
GSE72653

Methods Mentioned

BETA
biopsies
transfections
Feature Extraction
transfection
Assay
light microscopy

Software Mentioned

agilp
bioconductor
OneVsRestClassifier
Agilent Feature Extraction
R
Allred
ASW
rCGH
ggbiplot
FV10

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