Article
Homologous recombination deficiency and hemizygosity drive resistance in breast cancer.
Nature - 1 Apr 2026
Safonov Anton, Lee Minna, Brown David N, Boscolo Bielo Luca, Mehine Miika, Bandlamudi Chaitanya, O'Leary Ben, Shao Hong, Vicente Laia, Muldoon Daniel, Zhu Allen, Ros Susana, Marra Antonio, Selenica Pier, Bieche Ivan, Wubbenhorst Bradley, Ferraro Emanuela, Courtois Laura, El Botty Rania, Ahmed Mehnaj, Moiso Enrico, An Julia Ah-Reum, Donoghue Mark T A, Will Marie, Pareja Fresia, Nizialek Emily, Lukashchuk Natalia, Sofianopoulou Eleni, Liu Yuan, Huang Xin, Chappey Colombe, Staniszewska Anna D, Ross Dara, Mandelker Diana, Ladanyi Marc, Schultz Nikolaus, Berger Michael F, Scaltriti Maurizio, Reis-Filho Jorge S, Li Bob T, Offit Kenneth, Norton Larry, Shen Ronglai, Maxwell Kara N, Couch Fergus, Domchek Susan M, Marangoni Elisabetta, Shah Sohrab, Albertella Mark R, Serra Violeta, Weigelt Britta, Solit David B, Nathanson Katherine L, Robson Mark E, Turner Nicholas C, Chandarlapaty Sarat, Razavi Pedram
Abstract excerpt
The co-occurrence of germline and somatic oncogenic alterations is frequently observed in breast cancer, yet their combined influence on tumour evolution and therapy resistance remains poorly defined. Through an integrated clinicogenomic analysis of more than 5,800 patients, we show that germline (g) pathogenic variants dictate the evolutionary trajectory of acquired resistance. We specifically find that...
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