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Resistance to therapy caused by intragenic deletion in BRCA2

Author

Listed:
  • Stacey L. Edwards

    (The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK)

  • Rachel Brough

    (The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK)

  • Christopher J. Lord

    (The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK)

  • Rachael Natrajan

    (The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK)

  • Radost Vatcheva

    (The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK)

  • Douglas A. Levine

    (Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA)

  • Jeff Boyd

    (Anderson Cancer Institute, Memorial Health University Medical Center, 4700 Waters Avenue, Savannah, GA 31404, USA)

  • Jorge S. Reis-Filho

    (The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK)

  • Alan Ashworth

    (The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK)

Abstract

Resistance in BRCA2 cancers The platinum chemotherapeutics such as cisplatin and carboplatin are in clinical use in patients with BRCA2-mutated ovarian cancer. The initial response is generally good but most ovarian carcinomas ultimately become resistant to therapy. Two papers in this issue have identified a possible cause of this resistance as further mutation of the BRCA2 gene. Mutations in BRCA2 are associated with familial breast and ovarian cancer. Loss of BRCA2 function impairs DNA repair by homologous recombination and renders cells particular sensitive to cisplatin and also to PARP (poly (ADP-ribose) polymerase) inhibitors. The secondary 'resistance' mutations act by restoring the wild-type BRCA2 reading frame.

Suggested Citation

  • Stacey L. Edwards & Rachel Brough & Christopher J. Lord & Rachael Natrajan & Radost Vatcheva & Douglas A. Levine & Jeff Boyd & Jorge S. Reis-Filho & Alan Ashworth, 2008. "Resistance to therapy caused by intragenic deletion in BRCA2," Nature, Nature, vol. 451(7182), pages 1111-1115, February.
    • Handle: RePEc:nat:nature:v:451:y:2008:i:7182:d:10.1038_nature06548
    DOI: 10.1038/nature06548
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    Citations

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    Cited by:

    1. Fumiaki Ito & Ziyuan Li & Leonid Minakhin & Gurushankar Chandramouly & Mrityunjay Tyagi & Robert Betsch & John J. Krais & Bernadette Taberi & Umeshkumar Vekariya & Marissa Calbert & Tomasz Skorski & N, 2024. "Structural basis for a Polθ helicase small-molecule inhibitor revealed by cryo-EM," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Robert Appleby & Luay Joudeh & Katie Cobbett & Luca Pellegrini, 2023. "Structural basis for stabilisation of the RAD51 nucleoprotein filament by BRCA2," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. John Hilton & Karen Gelmon & Philippe L. Bedard & Dongsheng Tu & Hong Xu & Anna V. Tinker & Rachel Goodwin & Scott A. Laurie & Derek Jonker & Aaron R. Hansen & Zachary W. Veitch & Daniel J. Renouf & L, 2022. "Results of the phase I CCTG IND.231 trial of CX-5461 in patients with advanced solid tumors enriched for DNA-repair deficiencies," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Yuxin Huang & Wenjing Li & Tzeh Foo & Jae-Hoon Ji & Bo Wu & Nozomi Tomimatsu & Qingming Fang & Boya Gao & Melissa Long & Jingfei Xu & Rouf Maqbool & Bipasha Mukherjee & Tengyang Ni & Salvador Alejo & , 2024. "DSS1 restrains BRCA2’s engagement with dsDNA for homologous recombination, replication fork protection, and R-loop homeostasis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Yonina R. Murciano-Goroff & Alison M. Schram & Ezra Y. Rosen & Helen Won & Yixiao Gong & Anne Marie Noronha & Yelena Y. Janjigian & Zsofia K. Stadler & Jason C. Chang & Soo-Ryum Yang & Diana Mandelker, 2022. "Reversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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