Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma

TA Zwimpfer; S Fereday; A Pandey; D Ariyaratne; MW Jayawardana; L Twomey; CM Laumont; CJ Kennedy; A Bolithon; NS Meagher; K Milne; P Hamilton; J Alsop; AC Antoniou; G Au-Yeung; MW Beckmann; A Berrington de Gonzalez; C Bisinotto; F Blome; C Bodelon; J Boros; AH Brand; ME Carney; A Cazorla-Jiménez; DS Chiu; EL Christie; A Chudecka-Głaz; P Coulson; KL Cushing-Haugen; C Cybulski; KM Darcy; C David; T Davidson; AB Ekici; E Elishaev; J Emons; T Engler; R Farrell; A Fischer; M García-Closas; A Gentry-Maharaj; P Ghatage; R Glasspool; P Harter; AD Hartkopf; A Hartmann; S Heikaus; BY Hernandez; A Hettiaratchi; S Heublein; DG Huntsman; M Jimenez-Linan; ME Jones; E Kang; E Kaznowska; T Kluz; FKF Kommoss; G Konecny; RFPM Kruitwagen; J Kwon; D Lambrechts; CH Lee; J Lester; SCY Leung; Y Leung; A Linder; J Lissowska; L Loverix; J Lubiński; C Mateoiu; IA McNeish; M Moubarak; GS Nelson; N Nevins; AB Olawaiye; S Olbrecht; S Orsulic; A Osorio; CM Quinn; GR Mohan; I Ray-Coquard; C Rodríguez-Antona; P Roxburgh; M Ruebner; SG Salfinger; S Samra; MJ Schoemaker; HP Sinn; GS Sonke; L Steele; CJR Stewart; A Talhouk; A Tan; CM Tarney; SE Taylor; KK Van de Vijver; MA van der Aa; T Van Gorp; E Van Nieuwenhuysen; L Van-Wagensveld

Journal article

Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma

TA Zwimpfer, S Fereday, A Pandey, D Ariyaratne, MW Jayawardana, L Twomey, CM Laumont, CJ Kennedy, A Bolithon, NS Meagher, K Milne, P Hamilton, J Alsop, AC Antoniou, G Au-Yeung, MW Beckmann, A Berrington de Gonzalez, C Bisinotto, F Blome, C Bodelon Show all

Nature Communications | Published : 2026

DOI: 10.1038/s41467-026-71134-3

Open access

Abstract

BRCA-associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience poor outcomes. In a large HGSC cohort (n = 1389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), residual disease after primary surgery has limited prognostic effect in gBRCApv-carriers compared to non-carriers, and prognostic outcomes differ based on the mutation location within functional domains of the BRCA genes. Multi-omic profiling is performed on 154 tumors, enriched for patients with BRCA-defici..

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