Nicola Fusco
Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer
Fusco, Nicola; Geyer, Felipe C.; De Filippo, Maria R.; Martelotto, Luciano G.; Ng, Charlotte K.Y.; Piscuoglio, Salvatore; Guerini-Rocco, Elena; Schultheis, Anne M.; Fuhrmann, Laetitia; Wang, Lu; Jungbluth, Achim A.; Burke, Kathleen A.; Lim, Raymond S.; Vincent-Salomon, Anne; Bamba, Masamichi; Moritani, Suzuko; Badve, Sunil S.; Ichihara, Shu; Ellis, Ian O.; Reis-Filho, Jorge S.; Weigelt, Britta
Authors
Felipe C. Geyer
Maria R. De Filippo
Luciano G. Martelotto
Charlotte K.Y. Ng
Salvatore Piscuoglio
Elena Guerini-Rocco
Anne M. Schultheis
Laetitia Fuhrmann
Lu Wang
Achim A. Jungbluth
Kathleen A. Burke
Raymond S. Lim
Anne Vincent-Salomon
Masamichi Bamba
Suzuko Moritani
Sunil S. Badve
Shu Ichihara
Professor IAN ELLIS IAN.ELLIS@NOTTINGHAM.AC.UK
Professor of Cancer Pathology
Jorge S. Reis-Filho
Britta Weigelt
Abstract
Adenoid cystic carcinoma of the breast is a rare histological type of triple-negative breast cancer with an indolent clinical behavior, often driven by the MYB-NFIB fusion gene. Here we sought to define the repertoire of somatic genetic alterations in two adenoid cystic carcinomas associated with high-grade triple-negative breast cancer. The different components of each case were subjected to copy number profiling and massively parallel sequencing targeting all exons and selected regulatory and intronic regions of 488 genes. Reverse transcription PCR and fluorescence in situ hybridization were employed to investigate the presence of the MYB-NFIB translocation. The MYB-NFIB fusion gene was detected in both adenoid cystic carcinomas and their associated high-grade triple-negative breast cancer components. Although the distinct components of both cases displayed similar patterns of gene copy number alterations, massively parallel sequencing analysis revealed intratumor genetic heterogeneity. In case 1, progression from the trabecular adenoid cystic carcinoma to the high-grade triple-negative breast cancer was found to involve clonal shifts with enrichment of mutations affecting EP300, NOTCH1, ERBB2 and FGFR1 in the high-grade triple-negative breast cancer. In case 2, a clonal KMT2C mutation was present in the cribriform adenoid cystic carcinoma, solid adenoid cystic carcinoma and high-grade triple-negative breast cancer components, whereas a mutation affecting MYB was present only in the solid and high-grade triple-negative breast cancer areas and additional three mutations targeting STAG2, KDM6A and CDK12 were restricted to the high-grade triple-negative breast cancer. In conclusion, adenoid cystic carcinomas of the breast with high-grade transformation are underpinned by the MYB-NFIB fusion gene and, akin to other forms of cancer, may be constituted by a mosaic of cancer cell clones at diagnosis. The progression from adenoid cystic carcinoma to high-grade triple-negative breast cancer of no special type may involve the selection of neoplastic clones and/or the acquisition of additional genetic alterations.
Citation
Fusco, N., Geyer, F. C., De Filippo, M. R., Martelotto, L. G., Ng, C. K., Piscuoglio, S., …Weigelt, B. (2016). Genetic events in the progression of adenoid cystic carcinoma of the breast to high-grade triple-negative breast cancer. Modern Pathology, 29(11), 1292-1305. https://doi.org/10.1038/modpathol.2016.134
Journal Article Type | Article |
---|---|
Acceptance Date | May 31, 2016 |
Online Publication Date | Aug 5, 2016 |
Publication Date | Nov 30, 2016 |
Deposit Date | Aug 9, 2019 |
Journal | Modern Pathology |
Print ISSN | 0893-3952 |
Electronic ISSN | 1530-0285 |
Publisher | Nature Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 29 |
Issue | 11 |
Pages | 1292-1305 |
DOI | https://doi.org/10.1038/modpathol.2016.134 |
Keywords | Pathology and Forensic Medicine |
Public URL | https://nottingham-repository.worktribe.com/output/2411044 |
Publisher URL | https://www.nature.com/articles/modpathol2016134#main |
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