Rachel Joyce, Rosa Pascual, Luuk Heitink, Bianca D Capaldo, François Vaillant, Michael Christie, Minhsuang Tsai, Elliot Surgenor, Casey J A Anttila, Pradeep Rajasekhar, Felicity C Jackling, Marie Trussart, Michael J G Milevskiy, Xiaoyu Song, Mengbo Li, Charis E Teh, Daniel H D Gray, Gordon K Smyth, Yunshun Chen, Geoffrey J Lindeman, Jane E Visvader
Inheritance of a BRCA2 pathogenic variant conveys a substantial life-time risk of breast cancer. Identification of the cell(s)-of-origin of BRCA2-mutant breast cancer and targetable perturbations that contribute to transformation remains an unmet need for these individuals who frequently undergo prophylactic mastectomy. Using preneoplastic specimens from age-matched, premenopausal females, here we show broad dysregulation across the luminal compartment in BRCA2mut/+ tissue, including expansion of aberrant ERBB3lo luminal progenitor and mature cells, and the presence of atypical oestrogen receptor (ER)-positive lesions...
January 12, 2024: Nature Cell Biology