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

被引:13
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 Freddie, 2018, CA Cancer J Clin, V68, P394, DOI [10.3322/caac.21609, 10.3322/caac.21492]
  • [2] Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer
    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.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (26) : 2473 - 2483
  • [3] Improved survival in women with BRCA-associated ovarian carcinoma
    Cass, I
    Baldwin, RL
    Varkey, T
    Moslehi, R
    Narod, SA
    Karlan, BY
    [J]. CANCER, 2003, 97 (09) : 2187 - 2195
  • [4] 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)
  • [5] RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer
    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
    [J]. ANNALS OF ONCOLOGY, 2018, 29 (05) : 1203 - 1210
  • [6] Frequent Homologous Recombination Deficiency in High-grade Endometrial Carcinomas
    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
    [J]. 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
    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.
    [J]. 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)
    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
    [J]. 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.
    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
    [J]. 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
    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.
    [J]. CLINICAL CANCER RESEARCH, 2013, 19 (13) : 3474 - 3484