Медицинская библиотека · Nature communications · 2026
Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma.
Zwimpfer Tibor A, Fereday Sian, Pandey Ahwan, Ariyaratne Dinuka, Jayawardana Madawa W, Twomey Laura, Laumont Céline M, Kennedy Catherine J, Bolithon Adelyn, Meagher Nicola S, Milne Katy, Hamilton Phineas, Alsop Jennifer, Antoniou Antonis C, Au-Yeung George, Beckmann Matthias W, Berrington de Gonzalez Amy, Bisinotto Christiani, Blome Freya, Bodelon Clara, Boros Jessica, Brand Alison H, Carney Michael E, Cazorla-Jiménez Alicia, Chiu Derek S, Christie Elizabeth L, Chudecka-Głaz Anita, Coulson Penny, Cushing-Haugen Kara L, Cybulski Cezary, Darcy Kathleen M, David Cath, Davidson Trent, Ekici Arif B, Elishaev Esther, Emons Julius, Engler Tobias, Farrell Rhonda, Fischer Anna, García-Closas Montserrat, Gentry-Maharaj Aleksandra, Ghatage Prafull, Glasspool Rosalind, Harter Philipp, Hartkopf Andreas D, Hartmann Arndt, Heikaus Sebastian, Hernandez Brenda Y, Hettiaratchi Anusha, Heublein Sabine, Huntsman David G, Jimenez-Linan Mercedes, Jones Michael E, Kang Eunyoung, Kaznowska Ewa, Kluz Tomasz, Kommoss Felix K F, Konecny Gottfried, Kruitwagen Roy F P M, Kwon Jessica, Lambrechts Diether, Lee Cheng-Han, Lester Jenny, Leung Samuel C Y, Leung Yee, Linder Anna, Lissowska Jolanta, Loverix Liselore, Lubiński Jan, Mateoiu Constantina, McNeish Iain A, Moubarak Malak, Nelson Gregg S, Nevins Nikilyn, Olawaiye Alexander B, Olbrecht Siel, Orsulic Sandra, Osorio Ana, Quinn Carmel M, Mohan Ganendra Raj, Ray-Coquard Isabelle, Rodríguez-Antona Cristina, Roxburgh Patricia, Ruebner Matthias, Salfinger Stuart G, Samra Spinder, Schoemaker Minouk J, Sinn Hans-Peter, Sonke Gabe S, Steele Linda, Stewart Colin J R, Talhouk Aline, Tan Adeline, Tarney Christopher M, Taylor Sarah E, Van de Vijver Koen K, van der Aa Maaike A, Van Gorp Toon, Van Nieuwenhuysen Els, Van-Wagensveld Lilian, Wahner-Hendrickson Andrea E, Walter Christina, Wang Chen, Welz Julia, Wentzensen Nicolas, Wilkens Lynne R, Winham Stacey J, Winterhoff Boris, Anglesio Michael S, Berchuck Andrew, Candido Dos Reis Francisco J, Cohen Paul A, Conrads Thomas P, Crowe Philip, Doherty Jennifer A, Fasching Peter A, Fortner Renée T, García María J, Gayther Simon A, Goodman Marc T, Gronwald Jacek, Harris Holly R, Heitz Florian, Horlings Hugo M, Karlan Beth Y, Kelemen Linda E, Larry Maxwell G, Menon Usha, Modugno Francesmary, Neuhausen Susan L, Schildkraut Joellen M, Staebler Annette, Sundfeldt Karin, Swerdlow Anthony J, Vergote Ignace, Wu Anna H, Brenton James D, Pharoah Paul D P, Pearce Celeste Leigh, Pike Malcolm C, Goode Ellen L, Ramus Susan J, Köbel Martin, Nelson Brad H, DeFazio Anna, Friedlander Michael L, Bowtell David D L, Garsed Dale W
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Аннотация
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-deficient tumors that experienced short overall survival ( ≤ 3 years, n = 42). Patients with BRCA2-deficient HGSC and loss of NF1 survive twice as long as those without NF1 loss, whereas PIK3CA, RAD21 and MYC amplification define BRCA2-deficient HGSC with exceptionally short survival. Patients with BRCA1-deficient HGSC and a more elevated HRD score survive significantly longer. BRCA1-deficient tumors in short survivors have evidence of immunosuppressive c-kit signaling and EMT. Our findings confirm that outcome is not determined by BRCA status alone, but rather a combination of co-occurring genomic alterations, the extent of DNA repair deficiency, and the tumor-immune microenvironment.
Для цитирования: Zwimpfer Tibor A, Fereday Sian, Pandey Ahwan, Ariyaratne Dinuka, Jayawardana Madawa W, Twomey Laura, Laumont Céline M, Kennedy Catherine J, Bolithon Adelyn, Meagher Nicola S, Milne Katy, Hamilton Phineas, Alsop Jennifer, Antoniou Antonis C, Au-Yeung George, Beckmann Matthias W, Berrington de Gonzalez Amy, Bisinotto Christiani, Blome Freya, Bodelon Clara, Boros Jessica, Brand Alison H, Carney Michael E, Cazorla-Jiménez Alicia, Chiu Derek S, Christie Elizabeth L, Chudecka-Głaz Anita, Coulson Penny, Cushing-Haugen Kara L, Cybulski Cezary, Darcy Kathleen M, David Cath, Davidson Trent, Ekici Arif B, Elishaev Esther, Emons Julius, Engler Tobias, Farrell Rhonda, Fischer Anna, García-Closas Montserrat, Gentry-Maharaj Aleksandra, Ghatage Prafull, Glasspool Rosalind, Harter Philipp, Hartkopf Andreas D, Hartmann Arndt, Heikaus Sebastian, Hernandez Brenda Y, Hettiaratchi Anusha, Heublein Sabine, Huntsman David G, Jimenez-Linan Mercedes, Jones Michael E, Kang Eunyoung, Kaznowska Ewa, Kluz Tomasz, Kommoss Felix K F, Konecny Gottfried, Kruitwagen Roy F P M, Kwon Jessica, Lambrechts Diether, Lee Cheng-Han, Lester Jenny, Leung Samuel C Y, Leung Yee, Linder Anna, Lissowska Jolanta, Loverix Liselore, Lubiński Jan, Mateoiu Constantina, McNeish Iain A, Moubarak Malak, Nelson Gregg S, Nevins Nikilyn, Olawaiye Alexander B, Olbrecht Siel, Orsulic Sandra, Osorio Ana, Quinn Carmel M, Mohan Ganendra Raj, Ray-Coquard Isabelle, Rodríguez-Antona Cristina, Roxburgh Patricia, Ruebner Matthias, Salfinger Stuart G, Samra Spinder, Schoemaker Minouk J, Sinn Hans-Peter, Sonke Gabe S, Steele Linda, Stewart Colin J R, Talhouk Aline, Tan Adeline, Tarney Christopher M, Taylor Sarah E, Van de Vijver Koen K, van der Aa Maaike A, Van Gorp Toon, Van Nieuwenhuysen Els, Van-Wagensveld Lilian, Wahner-Hendrickson Andrea E, Walter Christina, Wang Chen, Welz Julia, Wentzensen Nicolas, Wilkens Lynne R, Winham Stacey J, Winterhoff Boris, Anglesio Michael S, Berchuck Andrew, Candido Dos Reis Francisco J, Cohen Paul A, Conrads Thomas P, Crowe Philip, Doherty Jennifer A, Fasching Peter A, Fortner Renée T, García María J, Gayther Simon A, Goodman Marc T, Gronwald Jacek, Harris Holly R, Heitz Florian, Horlings Hugo M, Karlan Beth Y, Kelemen Linda E, Larry Maxwell G, Menon Usha, Modugno Francesmary, Neuhausen Susan L, Schildkraut Joellen M, Staebler Annette, Sundfeldt Karin, Swerdlow Anthony J, Vergote Ignace, Wu Anna H, Brenton James D, Pharoah Paul D P, Pearce Celeste Leigh, Pike Malcolm C, Goode Ellen L, Ramus Susan J, Köbel Martin, Nelson Brad H, DeFazio Anna, Friedlander Michael L, Bowtell David D L, Garsed Dale W. Clinicopathologic and molecular predictors of survival in BRCA-deficient tubo-ovarian high-grade serous carcinoma.. Nature communications. 2026. DOI: 10.1038/s41467-026-71134-3.
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