IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39867-7.html
   My bibliography  Save this article

The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma

Author

Listed:
  • Philip Smith

    (CRUK Cambridge Institute, University of Cambridge)

  • Thomas Bradley

    (CRUK Cambridge Institute, University of Cambridge)

  • Lena Morrill Gavarró

    (CRUK Cambridge Institute, University of Cambridge)

  • Teodora Goranova

    (CRUK Cambridge Institute, University of Cambridge)

  • Darren P. Ennis

    (Imperial College London)

  • Hasan B. Mirza

    (Imperial College London)

  • Dilrini Silva

    (CRUK Cambridge Institute, University of Cambridge)

  • Anna M. Piskorz

    (CRUK Cambridge Institute, University of Cambridge)

  • Carolin M. Sauer

    (CRUK Cambridge Institute, University of Cambridge)

  • Sarwah Al-Khalidi

    (CRUK Cambridge Institute, University of Cambridge)

  • Ionut-Gabriel Funingana

    (CRUK Cambridge Institute, University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Marika A. V. Reinius

    (CRUK Cambridge Institute, University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Gaia Giannone

    (Imperial College London)

  • Liz-Anne Lewsley

    (University of Glasgow)

  • Jamie Stobo

    (University of Glasgow)

  • John McQueen

    (University of Glasgow)

  • Gareth Bryson

    (Queen Elizabeth University Hospital)

  • Matthew Eldridge

    (CRUK Cambridge Institute, University of Cambridge)

  • Geoff Macintyre

    (CRUK Cambridge Institute, University of Cambridge
    Centro Nacional de Investigaciones Oncológicas)

  • Florian Markowetz

    (CRUK Cambridge Institute, University of Cambridge)

  • James D. Brenton

    (CRUK Cambridge Institute, University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Iain A. McNeish

    (Imperial College London)

Abstract

The drivers of recurrence and resistance in ovarian high grade serous carcinoma remain unclear. We investigate the acquisition of resistance by collecting tumour biopsies from a cohort of 276 women with relapsed ovarian high grade serous carcinoma in the BriTROC-1 study. Panel sequencing shows close concordance between diagnosis and relapse, with only four discordant cases. There is also very strong concordance in copy number between diagnosis and relapse, with no significant difference in purity, ploidy or focal somatic copy number alterations, even when stratified by platinum sensitivity or prior chemotherapy lines. Copy number signatures are strongly correlated with immune cell infiltration, whilst diagnosis samples from patients with primary platinum resistance have increased rates of CCNE1 and KRAS amplification and copy number signature 1 exposure. Our data show that the ovarian high grade serous carcinoma genome is remarkably stable between diagnosis and relapse and acquired chemotherapy resistance does not select for common copy number drivers.

Suggested Citation

  • Philip Smith & Thomas Bradley & Lena Morrill Gavarró & Teodora Goranova & Darren P. Ennis & Hasan B. Mirza & Dilrini Silva & Anna M. Piskorz & Carolin M. Sauer & Sarwah Al-Khalidi & Ionut-Gabriel Funi, 2023. "The copy number and mutational landscape of recurrent ovarian high-grade serous carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39867-7
    DOI: 10.1038/s41467-023-39867-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39867-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39867-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ismael A. Vergara & Christopher P. Mintoff & Shahneen Sandhu & Lachlan McIntosh & Richard J. Young & Stephen Q. Wong & Andrew Colebatch & Daniel L. Cameron & Julia Lai Kwon & Rory Wolfe & Angela Peng , 2021. "Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Erik Dijk & Tom Bosch & Kristiaan J. Lenos & Khalid El Makrini & Lisanne E. Nijman & Hendrik F. B. Essen & Nico Lansu & Michiel Boekhout & Joris H. Hageman & Rebecca C. Fitzgerald & Cornelis J. A. Pun, 2021. "Chromosomal copy number heterogeneity predicts survival rates across cancers," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    3. S. Intidhar Labidi-Galy & Eniko Papp & Dorothy Hallberg & Noushin Niknafs & Vilmos Adleff & Michael Noe & Rohit Bhattacharya & Marian Novak & Siân Jones & Jillian Phallen & Carolyn A. Hruban & Michell, 2017. "High grade serous ovarian carcinomas originate in the fallopian tube," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    4. Olga Kondrashova & Monique Topp & Ksenija Nesic & Elizabeth Lieschke & Gwo-Yaw Ho & Maria I. Harrell & Giada V. Zapparoli & Alison Hadley & Robert Holian & Emma Boehm & Valerie Heong & Elaine Sanij & , 2018. "Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    5. Ruben M. Drews & Barbara Hernando & Maxime Tarabichi & Kerstin Haase & Tom Lesluyes & Philip S. Smith & Lena Morrill Gavarró & Dominique-Laurent Couturier & Lydia Liu & Michael Schneider & James D. Br, 2022. "A pan-cancer compendium of chromosomal instability," Nature, Nature, vol. 606(7916), pages 976-983, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Carolin M. Sauer & James A. Hall & Dominique-Laurent Couturier & Thomas Bradley & Anna M. Piskorz & Jacob Griffiths & Ashley Sawle & Matthew D. Eldridge & Philip Smith & Karen Hosking & Marika A. V. R, 2023. "Molecular landscape and functional characterization of centrosome amplification in ovarian cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Hongyu Shi & Marc J. Williams & Gryte Satas & Adam C. Weiner & Andrew McPherson & Sohrab P. Shah, 2024. "Allele-specific transcriptional effects of subclonal copy number alterations enable genotype-phenotype mapping in cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Rong Xiao & Deshu Xu & Meili Zhang & Zhanghua Chen & Li Cheng & Songjie Du & Mingfei Lu & Tonghai Zhou & Ruoyan Li & Fan Bai & Yue Huang, 2024. "Aneuploid embryonic stem cells drive teratoma metastasis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Marc A. Vittoria & Nathan Kingston & Kristyna Kotynkova & Eric Xia & Rui Hong & Lee Huang & Shayna McDonald & Andrew Tilston-Lunel & Revati Darp & Joshua D. Campbell & Deborah Lang & Xiaowei Xu & Crai, 2022. "Inactivation of the Hippo tumor suppressor pathway promotes melanoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Revati Darp & Marc A. Vittoria & Neil J. Ganem & Craig J. Ceol, 2022. "Oncogenic BRAF induces whole-genome doubling through suppression of cytokinesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Petra Brugge & Sarah C. Moser & Ivan Bièche & Petra Kristel & Sabrina Ibadioune & Alexandre Eeckhoutte & Roebi Bruijn & Eline Burg & Catrin Lutz & Stefano Annunziato & Julian Ruiter & Julien Masliah P, 2023. "Homologous recombination deficiency derived from whole-genome sequencing predicts platinum response in triple-negative breast cancers," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Jennifer B. Shah & Dana Pueschl & Bradley Wubbenhorst & Mengyao Fan & John Pluta & Kurt D’Andrea & Anna P. Hubert & Jake S. Shilan & Wenting Zhou & Adam A. Kraya & Alba Llop Guevara & Catherine Ruan &, 2022. "Analysis of matched primary and recurrent BRCA1/2 mutation-associated tumors identifies recurrence-specific drivers," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    8. Kristiaan J. Lenos & Sander Bach & Leandro Ferreira Moreno & Sanne Hoorn & Nina R. Sluiter & Sanne Bootsma & Felipe A. Vieira Braga & Lisanne E. Nijman & Tom Bosch & Daniel M. Miedema & Erik Dijk & Ba, 2022. "Molecular characterization of colorectal cancer related peritoneal metastatic disease," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Luisa Statello & José Miguel Fernandez-Justel & Jovanna González & Marta Montes & Alessia Ranieri & Enrique Goñi & Aina M. Mas & Maite Huarte, 2024. "The chromatin-associated lncREST ensures effective replication stress response by promoting the assembly of fork signaling factors," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Elena Denisenko & Leanne Kock & Adeline Tan & Aaron B. Beasley & Maria Beilin & Matthew E. Jones & Rui Hou & Dáithí Ó Muirí & Sanela Bilic & G. Raj K. A. Mohan & Stuart Salfinger & Simon Fox & Khaing , 2024. "Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39867-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.