A RAD51 functional assay as a candidate test for homologous recombination deficiency in ovarian cancer

被引:16
作者
Blanc-Durand, Felix [1 ]
Yaniz-Galende, Elisa [2 ]
Llop-Guevara, Alba [3 ]
Genestie, Catherine [4 ]
Serra, Violeta [3 ]
Herencia-Ropero, Andrea [3 ]
Klein, Christophe [5 ]
Berton, Dominique [6 ,7 ]
Lortholary, Alain [8 ]
Dohollou, Nadine [9 ]
Desauw, Christophe [10 ]
Fabbro, Michel [11 ]
Malaurie, Emmanuelle
Bonichon-Lamaichhane, Nathalie
Dubot, Coraline [12 ]
Kurtz, Jean Emmanuel
de Rauglaudre, Gaetan [13 ]
Raban, Nadia
Chevalier-Place, Annick [14 ]
Ferron, Gwenael [15 ]
Kaminsky, Marie-Christine [16 ]
Kramer, Claire
Rouleau, Etienne
Leary, Alexandra [1 ,2 ,17 ]
机构
[1] Gustave Roussy Inst, Gynecol Unit, Med Oncol, Villejuif, France
[2] Gustave Roussy Inst, INSERM UMR981, Villejuif, France
[3] Vall dHebron Inst Oncol, Expt Therapeut Grp, Barcelona, Spain
[4] Gustave Roussy Inst, Pathol Dept, Villejuif, France
[5] Cordeliers Res Ctr, Ctr Cellular Imaging & Cytometry, INSERM UMRS 1138, Paris, France
[6] GINECO, Med Oncol, St Herblain, France
[7] Inst Cancerol Ouest, St Herblain, France
[8] Hop Prive Confluent, Med Oncol, GINECO, Nantes, France
[9] Polyclin Bordeaux Nord Aquitain, Med Oncol, Bordeaux, France
[10] Ctr Hosp Univ, Med Oncol, Lille, France
[11] ICM Val dAurelle, Med Oncol, Montpellier, France
[12] Hop Rene Huguenin, Inst Curie, St Cloud, France
[13] Inst St Catherine, Avignon, France
[14] CHU Miletrie, Poitiers, France
[15] Inst Claudius Regaud, Toulouse, France
[16] Inst Cancerol Lorraine, Vandoeuvre Les Nancy, France
[17] Inst Gustave Roussy, Med Oncol Dept, Gynecol Unit, Lead Translat Res Team,INSERM U981, 114 Rue Edouard Vaillant, F-94800 Villejuif, France
关键词
Ovarian cancer; BRCA; EX-VIVO ASSAY; NEOADJUVANT CHEMOTHERAPY; PREDICTS RESPONSE; BEVACIZUMAB; SURVIVAL;
D O I
10.1016/j.ygyno.2023.01.026
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Rationale. Homologous recombination deficiency (HRD), defined as BRCA1/2 mutation (BRCAmut) or high genomic instability, is used to identify ovarian cancer (OC) patients most likely to benefit from PARP inhibitors. While these tests are useful, they are imperfect. Another approach is to measure the capacity of tumor cells to form RAD51 foci in the presence of DNA damage using an immunofluorescence assay (IF). We aimed to describe for the first time this assay in OC and correlate it to platinum response and BRCAmut.Methods. Tumor samples were prospectively collected from the randomized CHIVA trial of neoadjuvant plat-inum +/- nintedanib. IF for RAD51, GMN and gH2AX was performed on FFPE blocks. Tumors were considered RAD51-low if <= 10% of GMN-positive tumor cells had >= 5 RAD51 foci. BRCAmut were identified by NGS.
引用
收藏
页码:106 / 113
页数:8
相关论文
共 28 条
[1]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[2]   Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer [J].
Burger, Robert A. ;
Brady, Mark F. ;
Bookman, Michael A. ;
Fleming, Gini F. ;
Monk, Bradley J. ;
Huang, Helen ;
Mannel, Robert S. ;
Homesley, Howard D. ;
Fowler, Jeffrey ;
Greer, Benjamin E. ;
Boente, Matthew ;
Birrer, Michael J. ;
Liang, Sharon X. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (26) :2473-2483
[3]   Improved survival in women with BRCA-associated ovarian carcinoma [J].
Cass, I ;
Baldwin, RL ;
Varkey, T ;
Moslehi, R ;
Narod, SA ;
Karlan, BY .
CANCER, 2003, 97 (09) :2187-2195
[4]   A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation [J].
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 .
EMBO MOLECULAR MEDICINE, 2018, 10 (12)
[5]   RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer [J].
Cruz, C. ;
Castroviejo-Bermejo, M. ;
Gutierrez-Enriquez, S. ;
Llop-Guevara, A. ;
Ibrahim, Y. H. ;
Gris-Oliver, A. ;
Bonache, S. ;
Morancho, B. ;
Bruna, A. ;
Rueda, O. M. ;
Lai, Z. ;
Polanska, U. M. ;
Jones, G. N. ;
Kristel, P. ;
de Bustos, L. ;
Guzman, M. ;
Rodriguez, O. ;
Grueso, J. ;
Montalban, G. ;
Caratu, G. ;
Mancuso, F. ;
Fasani, R. ;
Jimenez, J. ;
Howat, W. J. ;
Dougherty, B. ;
Vivancos, A. ;
Nuciforo, P. ;
Serres-Creixams, X. ;
Rubio, I. T. ;
Oaknin, A. ;
Cadogan, E. ;
Barrett, J. C. ;
Caldas, C. ;
Baselga, J. ;
Saura, C. ;
Cortes, J. ;
Arribas, J. ;
Jonkers, J. ;
Diez, O. ;
O'Connor, M. J. ;
Balmana, J. ;
Serra, V .
ANNALS OF ONCOLOGY, 2018, 29 (05) :1203-1210
[6]   Frequent Homologous Recombination Deficiency in High-grade Endometrial Carcinomas [J].
de Jonge, Marthe M. ;
Auguste, Aurelie ;
van Wijk, Lise M. ;
Schouten, Philip C. ;
Meijers, Matty ;
ter Haar, Natalja T. ;
Smit, Vincent T. H. B. M. ;
Nout, Remi A. ;
Glaire, Mark A. ;
Church, David N. ;
Vrieling, Harry ;
Job, Bastien ;
Boursin, Yannick ;
de Kroon, Cor D. ;
Rouleau, Etienne ;
Leary, Alexandra ;
Vreeswijk, Maaike P. G. ;
Bosse, Tjalling .
CLINICAL CANCER RESEARCH, 2019, 25 (03) :1087-1097
[7]   Efficacy of Maintenance Olaparib for Patients With Newly Diagnosed Advanced Ovarian Cancer With a BRCA Mutation: Subgroup Analysis Findings From the SOLO1 Trial [J].
DiSilvestro, Paul ;
Colombo, Nicoletta ;
Scambia, Giovanni ;
Kim, Byoung-Gie ;
Oaknin, Ana ;
Friedlander, Michael ;
Lisyanskaya, Alla ;
Floquet, Anne ;
Leary, Alexandra ;
Sonke, Gabe S. ;
Gourley, Charlie ;
Banerjee, Susana ;
Oza, Amit ;
Gonzalez-Martin, Antonio ;
Aghajanian, Carol A. ;
Bradley, William H. ;
Mathews, Cara A. ;
Liu, Joyce ;
Lowe, Elizabeth S. ;
Bloomfield, Ralph ;
Moore, Kathleen N. .
JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (30) :3528-+
[8]   Survival analyses from a randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer with high tumor load (SCORPION trial) [J].
Fagotti, Anna ;
Vizzielli, Giuseppe ;
Ferrandina, Gabriella ;
Fanfani, Francesco ;
Gallotta, Valerio ;
Chiantera, Vito ;
Costantini, Barbara ;
Margariti, Pasquale Alessandro ;
Alletti, Salvatore Gueli ;
Cosentino, Francesco ;
Tortorella, Lucia ;
Scambia, Giovanni .
JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (15)
[9]   Impact of adding nintedanib to neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC) patients: The CHIVA double-blind randomized phase II GINECO study. [J].
Ferron, Gwenael ;
De Rauglaudre, Gaetan ;
Chevalier, Annick ;
Combe, Pierre ;
Joly, Florence ;
Lortholary, Alain ;
Raban, Nadia ;
Hamizi, Salima ;
Malaurie, Emmanuelle ;
Kaminsky, Marie-Christine ;
Pautier, Patricia ;
Meunier, Jerome ;
Alexandre, Jerome ;
Berton-Rigaud, Dominique ;
Floquet, Anne ;
Venat-Bouvet, Laurence ;
Favier, Laure ;
Dohollou, Nadine ;
Dubot, Coraline ;
Ray-Coquard, Isabelle Laure .
JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (15)
[10]   Nonequivalent Gene Expression and Copy Number Alterations in High-Grade Serous Ovarian Cancers with BRCA1 and BRCA2 Mutations [J].
George, Joshy ;
Alsop, Kathryn ;
Etemadmoghadam, Dariush ;
Hondow, Heather ;
Mikeska, Thomas ;
Dobrovic, Alexander ;
DeFazio, Anna ;
Smyth, Gordon K. ;
Levine, Douglas A. ;
Mitchell, Gillian ;
Bowtell, David D. .
CLINICAL CANCER RESEARCH, 2013, 19 (13) :3474-3484