Genomic and transcriptomic heterogeneity in metaplastic carcinomas of the breast

Piscuoglio, Salvatore and Ng, Charlotte K. Y. and Geyer, Felipe C. and Burke, Kathleen A. and Cowell, Catherine F. and Martelotto, Luciano G. and Natrajan, Rachael and Popova, Tatiana and Maher, Christopher A. and Lim, Raymond S. and Bruijn, Ino de and Mariani, Odette and Norton, Larry and Vincent-Salomon, Anne and Weigelt, Britta and Reis-Filho, Jorge S.. (2017) Genomic and transcriptomic heterogeneity in metaplastic carcinomas of the breast. NPJ Breast Cancer, 3. p. 48.

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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.
Faculties and Departments:03 Faculty of Medicine
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
UniBasel Contributors:Piscuoglio, Salvatore
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Research
Note:Publication type according to Uni Basel Research Database: Journal article
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edoc DOI:
Last Modified:06 Feb 2019 09:51
Deposited On:06 Feb 2019 09:51

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