Medicine and Health Sciences Commons^™

Recurrent Hotspot Mutations In Hras Q61 And Pi3k-Akt Pathway Genes As Drivers Of Breast Adenomyoepitheliomas., Felipe C. Geyer, Anqi Li, Anastasios D. Papanastasiou, Alison Smith, Pier Selenica, Kathleen A. Burke, Marcia Edelweiss, Huei-Chi Wen, Salvatore Piscuoglio, Anne M. Schultheis, Luciano G. Martelotto, Fresia Pareja, Rahul Kumar, Alissa Brandes, Dan Fan, Thais Basili, Arnaud Da Cruz Paula, John R. Lozada, Pedro Blecua, Simone Muenst, Achim A. Jungbluth, Maria P. Foschini, Hannah Y. Wen, Edi Brogi, Juan P. Palazzo, Brian P. Rubin, Charlotte K.Y. Ng, Larry Norton, Zsuzsanna Varga, Ian O. Ellis, Emad A. Rakha, Sarat Chandarlapaty, Britta Weigelt, Jorge S. Reis-Filho

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, whose genetic underpinning is largely unknown. Here we show through whole-exome and targeted massively parallel sequencing analysis that whilst estrogen receptor (ER)-positive adenomyoepitheliomas display PIK3CA or AKT1 activating mutations, ER-negative adenomyoepitheliomas harbor highly recurrent codon Q61 HRAS hotspot mutations, which co-occur with PIK3CA or PIK3R1 mutations. In two- and three-dimensional cell culture models, forced expression of HRAS