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

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 fr...

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Detalles Bibliográficos
Autores principales: Abdalla, Moustafa, Tran-Thanh, Danh, Moreno, Juan, Iakovlev, Vladimir, Nair, Ranju, Kanwar, Nisha, Abdalla, Mohamed, Lee, Jennifer P. Y., Kwan, Jennifer Yin Yee, Cawthorn, Thomas R., Warren, Keisha, Arneson, Nona, Wang, Dong-Yu, Fox, Natalie S., Youngson, Bruce J., Miller, Naomi A., Easson, Alexandra M., McCready, David, Leong, Wey L., Boutros, Paul C., Done, Susan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5665998/
https://www.ncbi.nlm.nih.gov/pubmed/29093438
http://dx.doi.org/10.1038/s41467-017-01357-y
Descripción
Sumario: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.