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14 results on '"Meijer, Titia G."'

2. Functional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests

Author

Meijer, Titia G., Nguyen, Luan, Van Hoeck, Arne, Sieuwerts, Anieta M., Verkaik, Nicole S., Ladan, Marjolijn M., Ruigrok-Ritstier, Kirsten, van Deurzen, Carolien H. M., van de Werken, Harmen J. G., Lips, Esther H., Linn, Sabine C., Memari, Yasin, Davies, Helen, Nik-Zainal, Serena, Kanaar, Roland, Martens, John W. M., Cuppen, Edwin, Jager, Agnes, and van Gent, Dik C.

Published
2022
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3. Functional Homologous Recombination (HR) Screening Shows the Majority of BRCA1/2 -Mutant Breast and Ovarian Cancer Cell Lines Are HR-Proficient.

Author

Meijer, Titia G., Martens, John W. M., Prager-van der Smissen, Wendy J. C., Verkaik, Nicole S., Beaufort, Corine M., van Herk, Stanley, Robert-Finestra, Teresa, Hoogenboezem, Remco M., Ruigrok-Ritstier, Kirsten, Paul, Maarten W., Gribnau, Joost, Bindels, Eric M. J., Kanaar, Roland, Jager, Agnes, van Gent, Dik C., and Hollestelle, Antoinette

Subjects
*OVARIAN tumors, *GENETIC mutation, *HOMOGRAFTS, *SEQUENCE analysis, *BRCA genes, *FUNCTIONAL status, *EARLY detection of cancer, *CELLS, *GENE expression profiling, *DESCRIPTIVE statistics, *METHYLATION, *RESEARCH funding, *CELL lines, *BREAST tumors
Abstract

Simple Summary: Cancer cells from patients who carry a disease-causing BRCA1 or BRCA2 mutation are incapable of repairing double-strand DNA breaks via the homologous recombination (HR) repair pathway. As a consequence, these patients respond to platinum-based chemotherapy and Poly-[ADP-Ribose]-Polymerase inhibitors (PARPi). However, using a functional read-out for HR, we show that not all HR-deficient cell lines carry a BRCA1/2 mutation. Moreover, the majority of BRCA1/2-mutant cell lines are HR proficient, highlighting the importance of measuring the functional HR status. For almost all of the BRCA1/2-mutant HR proficient cell lines, we could explain the discrepant HR status. The observed reversion mechanisms predominantly acted on restoring the BRCA1 or BRCA2 mutation directly. Taken together, our results indicate that only determining BRCA1/2 mutation status may not suffice for selecting patients for platinum-based chemotherapy or PARPi. Moreover, for experimental approaches cell line functionality of HR should be assessed beforehand. Tumors with a pathogenic BRCA1/2 mutation are homologous recombination (HR)-deficient (HRD) and consequently sensitive to platinum-based chemotherapy and Poly-[ADP-Ribose]-Polymerase inhibitors (PARPi). We hypothesized that functional HR status better reflects real-time HR status than BRCA1/2 mutation status. Therefore, we determined the functional HR status of 53 breast cancer (BC) and 38 ovarian cancer (OC) cell lines by measuring the formation of RAD51 foci after irradiation. Discrepancies between functional HR and BRCA1/2 mutation status were investigated using exome sequencing, methylation and gene expression data from 50 HR-related genes. A pathogenic BRCA1/2 mutation was found in 10/53 (18.9%) of BC and 7/38 (18.4%) of OC cell lines. Among BRCA1/2-mutant cell lines, 14/17 (82.4%) were HR-proficient (HRP), while 1/74 (1.4%) wild-type cell lines was HRD. For most (80%) cell lines, we explained the discrepancy between functional HR and BRCA1/2 mutation status. Importantly, 12/14 (85.7%) BRCA1/2-mutant HRP cell lines were explained by mechanisms directly acting on BRCA1/2. Finally, functional HR status was strongly associated with COSMIC single base substitution signature 3, but not BRCA1/2 mutation status. Thus, the majority of BRCA1/2-mutant cell lines do not represent a suitable model for HRD. Moreover, exclusively determining BRCA1/2 mutation status may not suffice for platinum-based chemotherapy or PARPi patient selection. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Supplemental legend from Functional Ex Vivo Assay Reveals Homologous Recombination Deficiency in Breast Cancer Beyond BRCA Gene Defects

Author

Meijer, Titia G., primary, Verkaik, Nicole S., primary, Sieuwerts, Anieta M., primary, van Riet, Job, primary, Naipal, Kishan A.T., primary, van Deurzen, Carolien H.M., primary, den Bakker, Michael A., primary, Sleddens, Hein F.B.M., primary, Dubbink, Hendrikus-Jan, primary, den Toom, T. Dorine, primary, Dinjens, Winand N.M., primary, Lips, Esther, primary, Nederlof, Petra M., primary, Smid, Marcel, primary, van de Werken, Harmen J.G., primary, Kanaar, Roland, primary, Martens, John W.M., primary, Jager, Agnes, primary, and van Gent, Dik C., primary

Published
2023
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5. Figure S3 from Functional Ex Vivo Assay Reveals Homologous Recombination Deficiency in Breast Cancer Beyond BRCA Gene Defects

Author

Meijer, Titia G., primary, Verkaik, Nicole S., primary, Sieuwerts, Anieta M., primary, van Riet, Job, primary, Naipal, Kishan A.T., primary, van Deurzen, Carolien H.M., primary, den Bakker, Michael A., primary, Sleddens, Hein F.B.M., primary, Dubbink, Hendrikus-Jan, primary, den Toom, T. Dorine, primary, Dinjens, Winand N.M., primary, Lips, Esther, primary, Nederlof, Petra M., primary, Smid, Marcel, primary, van de Werken, Harmen J.G., primary, Kanaar, Roland, primary, Martens, John W.M., primary, Jager, Agnes, primary, and van Gent, Dik C., primary

Published
2023
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6. Table S1, Table S2, Table S3 from Functional Ex Vivo Assay Reveals Homologous Recombination Deficiency in Breast Cancer Beyond BRCA Gene Defects

Author

Meijer, Titia G., primary, Verkaik, Nicole S., primary, Sieuwerts, Anieta M., primary, van Riet, Job, primary, Naipal, Kishan A.T., primary, van Deurzen, Carolien H.M., primary, den Bakker, Michael A., primary, Sleddens, Hein F.B.M., primary, Dubbink, Hendrikus-Jan, primary, den Toom, T. Dorine, primary, Dinjens, Winand N.M., primary, Lips, Esther, primary, Nederlof, Petra M., primary, Smid, Marcel, primary, van de Werken, Harmen J.G., primary, Kanaar, Roland, primary, Martens, John W.M., primary, Jager, Agnes, primary, and van Gent, Dik C., primary

Published
2023
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7. Abstract 805: RECAP (REpair CAPacity) identifies a subset of breast cancers unable to form RAD51 foci which are undetected by DNA-based BRCAness tests

Author

Meijer, Titia G., primary, Nguyen, Luan, additional, van Hoeck, Arne, additional, Ladan, Marjolijn M., additional, Verkaik, Nicole S., additional, Ruigrok-Ritstier, Kirsten, additional, van Deurzen, Carolien H., additional, van de Werken, Harmen J., additional, Lips, Esther H., additional, Linn, Sabine C., additional, Memari, Yasin, additional, Davies, Helen, additional, Nik-Zainal, Serena, additional, Kanaar, Roland, additional, Martens, John W., additional, Cuppen, Edwin, additional, Jager, Agnes, additional, and van Gent, Dik C., additional

Published
2022
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9. Direct Ex Vivo Observation of Homologous Recombination Defect Reversal After DNA-Damaging Chemotherapy in Patients With Metastatic Breast Cancer

Author

Meijer, Titia G., primary, Verkaik, Nicole S., additional, van Deurzen, Carolien H.M., additional, Dubbink, Hendrikus-Jan, additional, den Toom, T. Dorine, additional, Sleddens, Hein F.B.M., additional, De Hoop, Esther Oomen, additional, Dinjens, Winand N.M., additional, Kanaar, Roland, additional, van Gent, Dik C., additional, and Jager, Agnes, additional

Published
2019
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10. Correction: Functional Ex Vivo Assay Reveals Homologous Recombination Deficiency in Breast Cancer Beyond BRCA Gene Defects

Author

Meijer, Titia G., primary, Verkaik, Nicole S., additional, Sieuwerts, Anieta M., additional, van Riet, Job, additional, Naipal, Kishan A.T., additional, van Deurzen, Carolien H.M., additional, den Bakker, Michael A., additional, Sleddens, Hein F.B.M., additional, Dubbink, Hendrikus-Jan, additional, den Toom, T. Dorine, additional, Dinjens, Winand N.M., additional, Lips, Esther, additional, Nederlof, Petra M., additional, Smid, Marcel, additional, van de Werken, Harmen J.G., additional, Kanaar, Roland, additional, Martens, John W.M., additional, Jager, Agnes, additional, and van Gent, Dik C., additional

Published
2019
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11. Functional Ex Vivo Assay Reveals Homologous Recombination Deficiency in Breast Cancer Beyond BRCA Gene Defects

Author

Meijer, Titia G., primary, Verkaik, Nicole S., additional, Sieuwerts, Anieta M., additional, van Riet, Job, additional, Naipal, Kishan A.T., additional, van Deurzen, Carolien H.M., additional, den Bakker, Michael A., additional, Sleddens, Hein F.B.M., additional, Dubbink, Hendrikus-Jan, additional, den Toom, T. Dorine, additional, Dinjens, Winand N.M., additional, Lips, Esther, additional, Nederlof, Petra M., additional, Smid, Marcel, additional, van de Werken, Harmen J.G., additional, Kanaar, Roland, additional, Martens, John W.M., additional, Jager, Agnes, additional, and van Gent, Dik C., additional

Published
2018
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