naa a22 4500 555311198 20190207062214.0 cr unu---uuuuu 190207s2017 xx s 000 0 eng 2374-4677 10.1038/s41523-017-0048-0 doi (EDOC)oai:edoc.unibas.ch:68136 29214215 pmid Genomic and transcriptomic heterogeneity in metaplastic carcinomas of the breast [Elektronische Daten] [Salvatore Piscuoglio, Charlotte K. Y. Ng, Felipe C. Geyer, Kathleen A. Burke, Catherine F. Cowell, Luciano G. Martelotto, Rachael Natrajan, Tatiana Popova, Christopher A. Maher, Raymond S. Lim, Ino de Bruijn, Odette Mariani, Larry Norton, Anne Vincent-Salomon, Britta Weigelt, Jorge S. Reis-Filho] 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. Piscuoglio Salvatore joint author Ng Charlotte K. Y. joint author Geyer Felipe C. joint author Burke Kathleen A. joint author Cowell Catherine F. joint author Martelotto Luciano G. joint author Natrajan Rachael joint author Popova Tatiana joint author Maher Christopher A. joint author Lim Raymond S. joint author Bruijn Ino de joint author Mariani Odette joint author Norton Larry joint author Vincent-Salomon Anne joint author Weigelt Britta joint author Reis-Filho Jorge S. joint author NPJ Breast Cancer 3, p. 48 2374-4677 https://edoc.unibas.ch/68136/1/20190110093528_5c3703d0c1a9a.pdf text/html WWW-Backlink auf das Repository 1 Article edoc PeerReviewed edoc peerstatus EDOC 856 40 https://edoc.unibas.ch/68136/1/20190110093528_5c3703d0c1a9a.pdf text/html WWW-Backlink auf das Repository EDOC 700 1- Piscuoglio Salvatore joint author EDOC 700 1- Ng Charlotte K. Y. joint author EDOC 700 1- Geyer Felipe C. joint author EDOC 700 1- Burke Kathleen A. joint author EDOC 700 1- Cowell Catherine F. joint author EDOC 700 1- Martelotto Luciano G. joint author EDOC 700 1- Natrajan Rachael joint author EDOC 700 1- Popova Tatiana joint author EDOC 700 1- Maher Christopher A. joint author EDOC 700 1- Lim Raymond S. joint author EDOC 700 1- Bruijn Ino de joint author EDOC 700 1- Mariani Odette joint author EDOC 700 1- Norton Larry joint author EDOC 700 1- Vincent-Salomon Anne joint author EDOC 700 1- Weigelt Britta joint author EDOC 700 1- Reis-Filho Jorge S. joint author EDOC 773 0- NPJ Breast Cancer 3, p. 48 2374-4677 BK010053 XK010053 XK010000 EDOC EDOC EDOC Article