We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
FGFR4 overexpression and hotspot mutations in metastatic ER+ breast cancer are enriched in the lobular subtype.
- Authors
Levine, Kevin M.; Priedigkeit, Nolan; Basudan, Ahmed; Tasdemir, Nilgun; Sikora, Matthew J.; Sokol, Ethan S.; Hartmaier, Ryan J.; Ding, Kai; Ahmad, Nedah Z.; Watters, Rebecca J.; Weiss, Kurt R.; Blohmer, Jens-Uwe; Denkert, Carsten; Machleidt, Anna; Karsten, Maria M.; Boisen, Michelle M.; Elishaev, Esther; Lucas, Peter C.; Lee, Adrian V.; Oesterreich, Steffi
- Abstract
Invasive lobular carcinoma (ILC) is an understudied subtype of breast cancer that requires novel therapies in the advanced setting. To study acquired resistance to endocrine therapy in ILC, we have recently performed RNA-Sequencing on long-term estrogen deprived cell lines and identified FGFR4 overexpression as a top druggable target. Here, we show that FGFR4 expression also increases dramatically in endocrine-treated distant metastases, with an average fold change of 4.8 relative to the paired primary breast tumor for ILC, and 2.4-fold for invasive ductal carcinoma (IDC). In addition, we now report that FGFR4 hotspot mutations are enriched in metastatic breast cancer, with an additional enrichment for ILC, suggesting a multimodal selection of FGFR4 activation. These data collectively support the notion that FGFR4 is an important mediator of endocrine resistance in ILC, warranting future mechanistic studies on downstream signaling of overexpressed wild-type and mutant FGFR4.
- Publication
NPJ Breast Cancer, 2019, Vol 5, Issue 1, pN.PAG
- ISSN
2374-4677
- Publication type
Article
- DOI
10.1038/s41523-019-0114-x