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Characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer

BACKGROUND: Homologous recombination deficiency (HRD) is shown to predict response to DNA-damaging therapies in patients with high-grade serous ovarian cancer (HGSOC); however, changes in HRD during progression remains unknown. METHODS: HRD scores were evaluated in paired primary and/or recurrent HG...

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Autores principales: Patel, Jai N., Braicu, Ioana, Timms, Kirsten M., Solimeno, Cara, Tshiaba, Placede, Reid, Julia, Lanchbury, Jerry S., Darb-Esfahani, Silvia, Ganapathi, Mahrukh K., Sehouli, Jalid, Ganapathi, Ram N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219476/
https://www.ncbi.nlm.nih.gov/pubmed/30318511
http://dx.doi.org/10.1038/s41416-018-0268-6
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author Patel, Jai N.
Braicu, Ioana
Timms, Kirsten M.
Solimeno, Cara
Tshiaba, Placede
Reid, Julia
Lanchbury, Jerry S.
Darb-Esfahani, Silvia
Ganapathi, Mahrukh K.
Sehouli, Jalid
Ganapathi, Ram N.
author_facet Patel, Jai N.
Braicu, Ioana
Timms, Kirsten M.
Solimeno, Cara
Tshiaba, Placede
Reid, Julia
Lanchbury, Jerry S.
Darb-Esfahani, Silvia
Ganapathi, Mahrukh K.
Sehouli, Jalid
Ganapathi, Ram N.
author_sort Patel, Jai N.
collection PubMed
description BACKGROUND: Homologous recombination deficiency (HRD) is shown to predict response to DNA-damaging therapies in patients with high-grade serous ovarian cancer (HGSOC); however, changes in HRD during progression remains unknown. METHODS: HRD scores were evaluated in paired primary and/or recurrent HGSOC samples (N = 107) from 54 patients with adjuvant platinum-based chemotherapy. BRCA1/2 mutation, BRCA1 methylation, loss of heterozygosity (LOH), and HRD scores were characterised using tumour DNA-based next-generation sequencing assays. RESULTS: Among 50 evaluable pairs (N = 100 samples), high intra-patient correlation in HRD score was observed (r(2) = 0.93). BRCA1/2 mutations, BRCA1/2 LOH, and HRD were maintained between primary and recurrent samples, except for one pair in which a BRCA1 reversion mutation was identified in the recurrent sample. Despite the reversion, both samples were classified as having high HRD scores ( ≥ 42). All samples with BRCA1/2 mutations exhibited high HRD scores; however, high HRD scores were more prevalent than BRCA1/2 mutations (55% vs. 30%, respectively). CONCLUSION: Markers of HRD were maintained between the primary and recurrent samples, regardless of other genomic changes that occurred during recurrence. HRD score/markers in primary tumours may be valuable and adequate for selection of platinum-based therapy and/or poly-ADP-ribose-polymerase (PARP) inhibitors in recurrent HGSOC.
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spelling pubmed-62194762020-01-16 Characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer Patel, Jai N. Braicu, Ioana Timms, Kirsten M. Solimeno, Cara Tshiaba, Placede Reid, Julia Lanchbury, Jerry S. Darb-Esfahani, Silvia Ganapathi, Mahrukh K. Sehouli, Jalid Ganapathi, Ram N. Br J Cancer Article BACKGROUND: Homologous recombination deficiency (HRD) is shown to predict response to DNA-damaging therapies in patients with high-grade serous ovarian cancer (HGSOC); however, changes in HRD during progression remains unknown. METHODS: HRD scores were evaluated in paired primary and/or recurrent HGSOC samples (N = 107) from 54 patients with adjuvant platinum-based chemotherapy. BRCA1/2 mutation, BRCA1 methylation, loss of heterozygosity (LOH), and HRD scores were characterised using tumour DNA-based next-generation sequencing assays. RESULTS: Among 50 evaluable pairs (N = 100 samples), high intra-patient correlation in HRD score was observed (r(2) = 0.93). BRCA1/2 mutations, BRCA1/2 LOH, and HRD were maintained between primary and recurrent samples, except for one pair in which a BRCA1 reversion mutation was identified in the recurrent sample. Despite the reversion, both samples were classified as having high HRD scores ( ≥ 42). All samples with BRCA1/2 mutations exhibited high HRD scores; however, high HRD scores were more prevalent than BRCA1/2 mutations (55% vs. 30%, respectively). CONCLUSION: Markers of HRD were maintained between the primary and recurrent samples, regardless of other genomic changes that occurred during recurrence. HRD score/markers in primary tumours may be valuable and adequate for selection of platinum-based therapy and/or poly-ADP-ribose-polymerase (PARP) inhibitors in recurrent HGSOC. Nature Publishing Group UK 2018-10-15 2018-10-30 /pmc/articles/PMC6219476/ /pubmed/30318511 http://dx.doi.org/10.1038/s41416-018-0268-6 Text en © Cancer Research UK 2018 https://creativecommons.org/licenses/by-nc-sa/4.0/ This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License).
spellingShingle Article
Patel, Jai N.
Braicu, Ioana
Timms, Kirsten M.
Solimeno, Cara
Tshiaba, Placede
Reid, Julia
Lanchbury, Jerry S.
Darb-Esfahani, Silvia
Ganapathi, Mahrukh K.
Sehouli, Jalid
Ganapathi, Ram N.
Characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer
title Characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer
title_full Characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer
title_fullStr Characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer
title_full_unstemmed Characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer
title_short Characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer
title_sort characterisation of homologous recombination deficiency in paired primary and recurrent high-grade serous ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219476/
https://www.ncbi.nlm.nih.gov/pubmed/30318511
http://dx.doi.org/10.1038/s41416-018-0268-6
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