IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33870-0.html
   My bibliography  Save this article

Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer

Author

Listed:
  • Filipe Correia Martins

    (University of Cambridge
    University of Cambridge
    University of Cambridge
    The Francis Crick Institute)

  • Dominique-Laurent Couturier

    (University of Cambridge
    University of Cambridge)

  • Ines Santiago

    (University of Cambridge)

  • Carolin Margarethe Sauer

    (University of Cambridge)

  • Maria Vias

    (University of Cambridge)

  • Mihaela Angelova

    (The Francis Crick Institute)

  • Deborah Sanders

    (University of Cambridge)

  • Anna Piskorz

    (University of Cambridge)

  • James Hall

    (University of Cambridge)

  • Karen Hosking

    (Cambridge University Hospitals)

  • Anumithra Amirthanayagam

    (Cambridge University Hospitals)

  • Sabina Cosulich

    (Astrazeneca)

  • Larissa Carnevalli

    (Astrazeneca)

  • Barry Davies

    (Astrazeneca)

  • Thomas B. K. Watkins

    (The Francis Crick Institute)

  • Ionut G. Funingana

    (University of Cambridge
    University of Cambridge)

  • Helen Bolton

    (Cambridge University Hospitals)

  • Krishnayan Haldar

    (Cambridge University Hospitals)

  • John Latimer

    (Cambridge University Hospitals)

  • Peter Baldwin

    (Cambridge University Hospitals)

  • Robin Crawford

    (Cambridge University Hospitals)

  • Matthew Eldridge

    (University of Cambridge)

  • Bristi Basu

    (Cambridge University Hospitals
    University of Cambridge)

  • Mercedes Jimenez-Linan

    (Cambridge University Hospitals)

  • Andrew W. Mcpherson

    (Memorial Sloan Kettering Cancer Centre)

  • Nicholas McGranahan

    (University College London Cancer Institute)

  • Kevin Litchfield

    (The Francis Crick Institute)

  • Sohrab P. Shah

    (Memorial Sloan Kettering Cancer Centre)

  • Iain McNeish

    (Imperial College of London)

  • Carlos Caldas

    (University of Cambridge
    University of Cambridge)

  • Gerard Evan

    (University of Cambridge)

  • Charles Swanton

    (The Francis Crick Institute
    University College London Cancer Institute)

  • James D. Brenton

    (University of Cambridge
    University of Cambridge)

Abstract

Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identify five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reason that their strong selection should prioritise them as key biomarkers for targeted therapies. We use primary HGSOC spheroid models to test interactions between in vitro targeted therapy and SCNAs. MYC chromosomal copy number is associated with in-vitro and clinical response to paclitaxel and in-vitro response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context of MYC-amplified HGSOC is statistically associated with increased prevalence of SCNAs in genes from the PI3K pathway. Co-occurrence of amplifications in MYC and genes from the PI3K pathway is independently observed in squamous lung cancer and triple negative breast cancer. In this work, we show that identifying co-occurrence of clonal driver SCNA genes could be used to tailor therapeutics for precision medicine.

Suggested Citation

  • Filipe Correia Martins & Dominique-Laurent Couturier & Ines Santiago & Carolin Margarethe Sauer & Maria Vias & Mihaela Angelova & Deborah Sanders & Anna Piskorz & James Hall & Karen Hosking & Anumithr, 2022. "Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33870-0
    DOI: 10.1038/s41467-022-33870-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33870-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33870-0?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. Ankit Shukla & Thu H. M. Nguyen & Sarat B. Moka & Jonathan J. Ellis & John P. Grady & Harald Oey & Alexandre S. Cristino & Kum Kum Khanna & Dirk P. Kroese & Lutz Krause & Eloise Dray & J. Lynn Fink & , 2020. "Chromosome arm aneuploidies shape tumour evolution and drug response," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Arkajyoti Bhattacharya & Rico D. Bense & Carlos G. Urzúa-Traslaviña & Elisabeth G. E. Vries & Marcel A. T. M. Vugt & Rudolf S. N. Fehrmann, 2020. "Transcriptional effects of copy number alterations in a large set of human cancers," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Louisa Nelson & Anthony Tighe & Anya Golder & Samantha Littler & Bjorn Bakker & Daniela Moralli & Syed Murtuza Baker & Ian J. Donaldson & Diana C. J. Spierings & René Wardenaar & Bethanie Neale & Geor, 2020. "A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    4. Ann-Marie Patch & Elizabeth L. Christie & Dariush Etemadmoghadam & Dale W. Garsed & Joshy George & Sian Fereday & Katia Nones & Prue Cowin & Kathryn Alsop & Peter J. Bailey & Karin S. Kassahn & Felici, 2015. "Whole–genome characterization of chemoresistant ovarian cancer," Nature, Nature, vol. 521(7553), pages 489-494, May.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. 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.

    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. Yi-Yu Chen & Jing-Yu Ge & Si-Yuan Zhu & Zhi-Ming Shao & Ke-Da Yu, 2022. "Copy number amplification of ENSA promotes the progression of triple-negative breast cancer via cholesterol biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Adam C. Weiner & Marc J. Williams & Hongyu Shi & Ignacio Vázquez-García & Sohrab Salehi & Nicole Rusk & Samuel Aparicio & Sohrab P. Shah & Andrew McPherson, 2024. "Inferring replication timing and proliferation dynamics from single-cell DNA sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Liujia Qian & Jianqing Zhu & Zhangzhi Xue & Yan Zhou & Nan Xiang & Hong Xu & Rui Sun & Wangang Gong & Xue Cai & Lu Sun & Weigang Ge & Yufeng Liu & Ying Su & Wangmin Lin & Yuecheng Zhan & Junjian Wang , 2024. "Proteomic landscape of epithelial ovarian cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. 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.
    5. 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.
    6. Mireia Crispin-Ortuzar & Ramona Woitek & Marika A. V. Reinius & Elizabeth Moore & Lucian Beer & Vlad Bura & Leonardo Rundo & Cathal McCague & Stephan Ursprung & Lorena Escudero Sanchez & Paula Martin-, 2023. "Integrated radiogenomics models predict response to neoadjuvant chemotherapy in high grade serous ovarian cancer," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    7. Chunman Zuo & Yijian Zhang & Chen Cao & Jinwang Feng & Mingqi Jiao & Luonan Chen, 2022. "Elucidating tumor heterogeneity from spatially resolved transcriptomics data by multi-view graph collaborative learning," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Tom Nyen & Mélanie Planque & Lilian Wagensveld & Joao A. G. Duarte & Esther A. Zaal & Ali Talebi & Matteo Rossi & Pierre-René Körner & Lara Rizzotto & Stijn Moens & Wout Wispelaere & Regina E. M. Baid, 2022. "Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    9. 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.
    10. Qilin Zhang & Ziyan Xu & Rui Han & Yunzhi Wang & Zhen Ye & Jiajun Zhu & Yixin Cai & Fan Zhang & Jiangyan Zhao & Boyuan Yao & Zhaoyu Qin & Nidan Qiao & Ruofan Huang & Jinwen Feng & Yongfei Wang & Wenti, 2024. "Proteogenomic characterization of skull-base chordoma," Nature Communications, Nature, vol. 15(1), pages 1-32, December.
    11. Chunyang Bao & Richard W. Tourdot & Gregory J. Brunette & Chip Stewart & Lili Sun & Hideo Baba & Masayuki Watanabe & Agoston T. Agoston & Kunal Jajoo & Jon M. Davison & Katie S. Nason & Gad Getz & Ken, 2023. "Genomic signatures of past and present chromosomal instability in Barrett’s esophagus and early esophageal adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    12. Dan Daniel Erdmann-Pham & Sanjit Singh Batra & Timothy K. Turkalo & James Durbin & Marco Blanchette & Iwei Yeh & Hunter Shain & Boris C. Bastian & Yun S. Song & Daniel S. Rokhsar & Dirk Hockemeyer, 2023. "Tracing cancer evolution and heterogeneity using Hi-C," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. Leanne M. Brown & Ryan A. Hagenson & Tilen Koklič & Iztok Urbančič & Lu Qiao & Janez Strancar & Jason M. Sheltzer, 2024. "An elevated rate of whole-genome duplications in cancers from Black patients," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    14. Dario Zimmerli & Chiara S. Brambillasca & Francien Talens & Jinhyuk Bhin & Renske Linstra & Lou Romanens & Arkajyoti Bhattacharya & Stacey E. P. Joosten & Ana Moises Silva & Nuno Padrao & Max D. Welle, 2022. "MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    15. Chunge Zhong & Wen-Jie Jiang & Yingjia Yao & Zexu Li & You Li & Shengnan Wang & Xiaofeng Wang & Wenjuan Zhu & Siqi Wu & Jing Wang & Shuangshuang Fan & Shixin Ma & Yeshu Liu & Han Zhang & Wenchang Zhao, 2024. "CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    16. 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:13:y:2022:i:1:d:10.1038_s41467-022-33870-0. 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.