Homologous recombination repair status in metastatic prostate cancer by next-generation sequencing and functional immunofluorescence

被引：0

作者：

Arce-Gallego, Sara ^{[1
]}

Morgado, Pablo Cresta ^{[1
,2
]}

Delgado-Serrano, Luisa ^{[1
]}

Simonetti, Sara ^{[3
]}

Gonzalez, Macarena ^{[1
,4
,5
]}

Romero-Lozano, Paula ^{[6
]}

Marmolejo, David ^{[1
,4
,5
]}

Morales-Barrera, Rafael ^{[1
,4
,5
]}

Arnau, Gisela Mir ^{[1
]}

Semidey, Maria Eugenia ^{[7
]}

Aguilar, Daniel ^{[1
]}

Cordoba-Terreros, Sarai ^{[1
]}

Mast, Richard ^{[8
]}

de Albert, Matias ^{[8
]}

Planas, Jacques ^{[9
]}

Cuadras, Merce ^{[9
]}

Maldonado, Xavier ^{[10
]}

Suarez, Cristina ^{[1
,4
,5
]}

Casanova-Salas, Irene ^{[1
]}

Figols, Mariona ^{[11
]}

Cros, Sara ^{[12
]}

Mas, Alba ^{[13
]}

Nonell, Lara ^{[13
]}

Dienstmann, Rodrigo ^{[2
,14
]}

Nuciforo, Paolo ^{[3
]}

Vivancos, Ana ^{[6
]}

Llop-Guevara, Alba ^{[15
]}

Carles, Joan ^{[1
,4
,5
]}

Serra, Violeta ^{[15
]}

Mateo, Joaquin ^{[1
,4
,5
]}

机构：

[1] Vall dHebron Inst Oncol VHIO, Cellex Ctr, Natzaret 115-117, Barcelona 08035, Spain

[2] Vall dHebron Inst Oncol VHIO, Oncol Data Sci ODysSey Grp, Barcelona, Spain

[3] Vall dHebron Inst Oncol VHIO, Mol Oncol, Barcelona, Spain

[4] Vall DHebron Univ Hosp, Vall DHebron Inst Oncol VHIO, Barcelona, Spain

[5] Vall dHebron Inst Oncol VHIO, Barcelona, Spain

[6] Vall dHebron Inst Oncol VHIO, Canc Genom Grp, Barcelona, Spain

[7] Vall dHebron Univ Hosp, Dept Pathol, Barcelona, Spain

[8] Vall dHebron Univ Hosp, Dept Radiol, Barcelona, Spain

[9] Vall dHebron Univ Hosp, Dept Urol, Barcelona, Spain

[10] Vall dHebron Univ Hosp, Dept Radiat Oncol, Barcelona, Spain

[11] Althaia Xarxa Assistencial Univ Manresa, Dept Med Oncol, Manresa, Spain

[12] Granollers Hosp, Dept Med Oncol, Granollers, Spain

[13] Vall dHebron Inst Oncol VHIO, Bioinformat Unit, Barcelona, Spain

[14] Univ Vic, Cent Univ Catalonia, Vic, Spain

[15] Vall dHebron Inst Oncol VHIO, Expt Therapeut Grp, Barcelona, Spain

来源：

CELL REPORTS | 2025年 / 6卷 / 02期

关键词：

DNA-REPAIR; DEFICIENCY; GENOMICS; OLAPARIB; DEFECTS; TUMORS; RAD51;

D O I：

10.1016/j.xcrm.2025.101937

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Metastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations, which have prognostic and predictive value. Routine clinical implementation of next-generation sequencing (NGS) is still limited. We investigated the association between genomic and functional loss of HRR, using NGS and RAD51 immunofluorescence (RAD51-IF) in 219 primary or metastatic biopsies from 187 patients with stage IV prostate cancer. NGS showed frequent genomic alterations in TP53 (40%), AR (15%), PTEN (14%), FOXA1 (12%), MYC (10%), BRCA2 (9%), ATM (8%), and BRCA1 (2%). We pursued RAD51-IF in 206 samples; of those, 139/206 (67%) were evaluable. 21% of samples had RAD51-low score compatible with HRR deficiency (HRD). RAD51-IF showed high sensitivity (71%) and specificity (86%) for BRCA1/2 alterations. Patients with RAD51-low scores experienced longer progression-free survival (PFS) on poly(ADPribose) polymerase inhibitors (PARPi) or platinum chemotherapy. RAD51-IF is feasible in routine clinical samples from patients with mPC and is associated with clinically relevant HRR gene alterations.

引用

页数：16

共 69 条

[1] The Molecular Taxonomy of Primary Prostate Cancer
Abeshouse, Adam
Ahn, Jaeil
Akbani, Rehan
Ally, Adrian
Amin, Samirkumar
Andry, Christopher D.
Annala, Matti
Aprikian, Armen
Armenia, Joshua
Arora, Arshi
Auman, J. Todd
Balasundaram, Miruna
Balu, Saianand
Barbieri, Christopher E.
Bauer, Thomas
Benz, Christopher C.
Bergeron, Alain
Beroukhim, Rameen
Berrios, Mario
Bivol, Adrian
Bodenheimer, Tom
Boice, Lori
Bootwalla, Moiz S.
dos Reis, Rodolfo Borges
Boutros, Paul C.
Bowen, Jay
Bowlby, Reanne
Boyd, Jeffrey
Bradley, Robert K.
Breggia, Anne
Brimo, Fadi
Bristow, Christopher A.
Brooks, Denise
Broom, Bradley M.
Bryce, Alan H.
Bubley, Glenn
Burks, Eric
Butterfield, Yaron S. N.
Button, Michael
Canes, David
Carlotti, Carlos G.
Carlsen, Rebecca
Carmel, Michel
Carroll, Peter R.
Carter, Scott L.
Cartun, Richard
Carver, Brett S.
Chan, June M.
Chang, Matthew T.
Chen, Yu
[J]. CELL, 2015, 163 (04) : 1011 - 1025
[2] Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making
Abida, Wassim
Armenia, Joshua
Gopalan, Anuradha
Brennan, Ryan
Walsh, Michael
Barron, David
Danila, Daniel
Rathkopf, Dana
Morris, Michael
Slovin, Susan
McLaughlin, Brigit
Curtis, Kristen
Hyman, David M.
Durack, Jeremy C.
Solomon, Stephen B.
Arcila, Maria E.
Zehir, Ahmet
Syed, Aijazuddin
Gao, Jianjiong
Chakravarty, Debyani
Vargas, Hebert Alberto
Robson, Mark E.
Vijai, Joseph
Offit, Kenneth
Donoghue, Mark T. A.
Abeshouse, Adam A.
Kundra, Ritika
Heins, Zachary J.
Penson, Alexander V.
Harris, Christopher
Taylor, Barry S.
Ladanyi, Marc
Mandelker, Diana
Zhang, Liying
Reuter, Victor E.
Kantoff, Philip W.
Solit, David B.
Berger, Michael F.
Sawyers, Charles L.
Schultz, Nikolaus
Scher, Howard I.
[J]. JCO PRECISION ONCOLOGY, 2017, 1 : 1 - 26
[3] Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer
Abkevich, V.
Timms, K. M.
Hennessy, B. T.
Potter, J.
Carey, M. S.
Meyer, L. A.
Smith-McCune, K.
Broaddus, R.
Lu, K. H.
Chen, J.
Tran, T. V.
Williams, D.
Iliev, D.
Jammulapati, S.
FitzGerald, L. M.
Krivak, T.
DeLoia, J. A.
Gutin, A.
Mills, G. B.
Lanchbury, J. S.
[J]. BRITISH JOURNAL OF CANCER, 2012, 107 (10) : 1776 - 1782
[4] Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors
Adalsteinsson, Viktor A.
Ha, Gavin
Freeman, Samuel S.
Choudhury, Atish D.
Stover, Daniel G.
Parsons, Heather A.
Gydush, Gregory
Reed, Sarah C.
Rotem, Denisse
Rhoades, Justin
Loginov, Denis
Livitz, Dimitri
Rosebrock, Daniel
Leshchiner, Ignaty
Kim, Jaegil
Stewart, Chip
Rosenberg, Mara
Francis, Joshua M.
Zhang, Cheng-Zhong
Cohen, Ofir
Oh, Coyin
Ding, Huiming
Polak, Paz
Lloyd, Max
Mahmud, Sairah
Helvie, Karla
Merrill, Margaret S.
Santiago, Rebecca A.
O'Connor, Edward P.
Jeong, Seong H.
Leeson, Rachel
Barry, Rachel M.
Kramkowski, Joseph F.
Zhang, Zhenwei
Polacek, Laura
Lohr, Jens G.
Schleicher, Molly
Lipscomb, Emily
Saltzman, Andrea
Oliver, Nelly M.
Marini, Lori
Waks, Adrienne G.
Harshman, Lauren C.
Tolaney, Sara M.
Van Allen, Eliezer M.
Winer, Eric P.
Lin, Nancy U.
Nakabayashi, Mari
Taplin, Mary-Ellen
Johannessen, Cory M.
[J]. NATURE COMMUNICATIONS, 2017, 8
[5] Arce-Gallego S, 2024, bioRxiv, DOI [10.1101/2024.01.28.577367, 10.1101/2024.01.28.577367, DOI 10.1101/2024.01.28.577367]
[6] Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents
Birkbak, Nicolai J.
Wang, Zhigang C.
Kim, Ji-Young
Eklund, Aron C.
Li, Qiyuan
Tian, Ruiyang
Bowman-Colin, Christian
Li, Yang
Greene-Colozzi, April
Iglehart, J. Dirk
Tung, Nadine
Ryan, Paula D.
Garber, Judy E.
Silver, Daniel P.
Szallasi, Zoltan
Richardson, Andrea L.
[J]. CANCER DISCOVERY, 2012, 2 (04) : 366 - 375
[7] Boutros Paul, 2022, CRAN
[8] Breiman L., 2022, Preprints
[9] Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial
Carreira, Suzanne
Porta, Nuria
Arce-Gallego, Sara
Seed, George
Llop-Guevara, Alba
Bianchini, Diletta
Rescigno, Pasquale
Paschalis, Alec
Bertan, Claudia
Baker, Chloe
Goodall, Jane
Miranda, Susana
Riisnaes, Ruth
Figueiredo, Ines
Ferreira, Ana
Pereira, Rita
Crespo, Mateus
Gurel, Bora
Rodrigues, Daniel Nava
Pettitt, Stephen J.
Yuan, Wei
Serra, Violeta
Rekowski, Jan
Lord, Christopher J.
Hall, Emma
Mateo, Joaquin
de Bono, Johann S.
[J]. CANCER DISCOVERY, 2021, 11 (11) : 2812 - 2827
[10] A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation
Castroviejo-Bermejo, Marta
Cruz, Cristina
Llop-Guevara, Alba
Gutierrez-Enriquez, Sara
Ducy, Mandy
Hussein Ibrahim, Yasir
Gris-Oliver, Albert
Pellegrino, Benedetta
Bruna, Alejandra
Guzman, Marta
Rodriguez, Olga
Grueso, Judit
Bonache, Sandra
Moles-Fernandez, Alejandro
Villacampa, Guillermo
Viaplana, Cristina
Gomez, Patricia
Vidal, Marc
Peg, Vicente
Serres-Creixams, Xavier
Dellaire, Graham
Simard, Jacques
Nuciforo, Paolo
Rubio, Isabel T.
Dientsmann, Rodrigo
Barrett, J. Carl
Caldas, Carlos
Baselga, Jose
Saura, Cristina
Cortes, Javier
Deas, Olivier
Jonkers, Jos
Masson, Jean-Yves
Cairo, Stefano
Judde, Jean-Gabriel
O'Connor, Mark J.
Diez, Orland
Balmana, Judith
Serra, Violeta
[J]. EMBO MOLECULAR MEDICINE, 2018, 10 (12)

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