dc.contributor.author | Piscuoglio, S | |
dc.contributor.author | Ng, CKY | |
dc.contributor.author | Geyer, FC | |
dc.contributor.author | Burke, KA | |
dc.contributor.author | Cowell, CF | |
dc.contributor.author | Martelotto, LG | |
dc.contributor.author | Natrajan, R | |
dc.contributor.author | Popova, T | |
dc.contributor.author | Maher, CA | |
dc.contributor.author | Lim, RS | |
dc.contributor.author | Bruijn, ID | |
dc.contributor.author | Mariani, O | |
dc.contributor.author | Norton, L | |
dc.contributor.author | Vincent-Salomon, A | |
dc.contributor.author | Weigelt, B | |
dc.contributor.author | Reis-Filho, JS | |
dc.date.accessioned | 2021-03-01T14:10:15Z | |
dc.date.available | 2021-03-01T14:10:15Z | |
dc.date.issued | 2017-12-01 | |
dc.identifier.citation | NPJ breast cancer, 2017, 3 pp. 48 - ? | |
dc.identifier.issn | 2374-4677 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4372 | |
dc.identifier.eissn | 2374-4677 | |
dc.identifier.doi | 10.1038/s41523-017-0048-0 | |
dc.description.abstract | Metaplastic breast cancer (MBC) is a rare special histologic type of triple-negative breast cancer, characterized by the presence of neoplastic cells showing differentiation towards squamous epithelium and/or mesenchymal elements. Here we sought to define whether histologically distinct subgroups of MBCs would be underpinned by distinct genomic and/or transcriptomic alterations. Microarray-based copy number profiling identified limited but significant differences between the distinct MBC subtypes studied here, despite the limited sample size (n = 17). In particular, we found that, compared to MBCs with chondroid or squamous cell metaplasia, MBCs with spindle cell differentiation less frequently harbored gain of 7q11.22-23 encompassing CLDN3 and CLDN4, consistent with their lower expression of claudins and their association with the claudin-low molecular classification. Microarray-based and RNA-sequencing-based gene expression profiling revealed that MBCs with spindle cell differentiation differ from MBCs with chondroid or squamous cell metaplasia on the expression of epithelial-to-mesenchymal transition-related genes, including down-regulation of CDH1 and EPCAM. In addition, RNA-sequencing revealed that the histologic patterns observed in MBCs are unlikely to be underpinned by a highly recurrent expressed fusion gene or a pathognomonic expressed mutation in cancer genes. Loss of PTEN expression or mutations affecting PIK3CA or TSC2 observed in 8/17 MBCs support the contention that PI3K pathway activation plays a role in the development of MBCs. Our data demonstrate that despite harboring largely similar patterns of gene copy number alterations, MBCs with spindle cell, chondroid and squamous differentiation are distinct at the transcriptomic level but are unlikely to be defined by specific pathognomonic genetic alterations. | |
dc.format | Electronic-eCollection | |
dc.format.extent | 48 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Genomic and transcriptomic heterogeneity in metaplastic carcinomas of the breast. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-10-19 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41523-017-0048-0 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | NPJ breast cancer | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics | |
pubs.publication-status | Published | |
pubs.volume | 3 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Functional Genomics | |
icr.researchteam | Functional Genomics | |
dc.contributor.icrauthor | Natrajan, Rachael | |