IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0081843.html
   My bibliography  Save this article

Candidate Luminal B Breast Cancer Genes Identified by Genome, Gene Expression and DNA Methylation Profiling

Author

Listed:
  • Stéphanie Cornen
  • Arnaud Guille
  • José Adélaïde
  • Lynda Addou-Klouche
  • Pascal Finetti
  • Marie-Rose Saade
  • Marwa Manai
  • Nadine Carbuccia
  • Ismahane Bekhouche
  • Anne Letessier
  • Stéphane Raynaud
  • Emmanuelle Charafe-Jauffret
  • Jocelyne Jacquemier
  • Salvatore Spicuglia
  • Hugues de The
  • Patrice Viens
  • François Bertucci
  • Daniel Birnbaum
  • Max Chaffanet

Abstract

Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15) and UTRN (6q24), were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype.

Suggested Citation

  • Stéphanie Cornen & Arnaud Guille & José Adélaïde & Lynda Addou-Klouche & Pascal Finetti & Marie-Rose Saade & Marwa Manai & Nadine Carbuccia & Ismahane Bekhouche & Anne Letessier & Stéphane Raynaud & E, 2014. "Candidate Luminal B Breast Cancer Genes Identified by Genome, Gene Expression and DNA Methylation Profiling," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-16, January.
    • Handle: RePEc:plo:pone00:0081843
    DOI: 10.1371/journal.pone.0081843
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081843
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0081843&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0081843?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. Matthew J. Ellis & Li Ding & Dong Shen & Jingqin Luo & Vera J. Suman & John W. Wallis & Brian A. Van Tine & Jeremy Hoog & Reece J. Goiffon & Theodore C. Goldstein & Sam Ng & Li Lin & Robert Crowder & , 2012. "Whole-genome analysis informs breast cancer response to aromatase inhibition," Nature, Nature, vol. 486(7403), pages 353-360, June.
    2. Charles M. Perou & Therese Sørlie & Michael B. Eisen & Matt van de Rijn & Stefanie S. Jeffrey & Christian A. Rees & Jonathan R. Pollack & Douglas T. Ross & Hilde Johnsen & Lars A. Akslen & Øystein Flu, 2000. "Molecular portraits of human breast tumours," Nature, Nature, vol. 406(6797), pages 747-752, August.
    3. Sohrab P. Shah & Andrew Roth & Rodrigo Goya & Arusha Oloumi & Gavin Ha & Yongjun Zhao & Gulisa Turashvili & Jiarui Ding & Kane Tse & Gholamreza Haffari & Ali Bashashati & Leah M. Prentice & Jaswinder , 2012. "The clonal and mutational evolution spectrum of primary triple-negative breast cancers," Nature, Nature, vol. 486(7403), pages 395-399, June.
    4. Shantanu Banerji & Kristian Cibulskis & Claudia Rangel-Escareno & Kristin K. Brown & Scott L. Carter & Abbie M. Frederick & Michael S. Lawrence & Andrey Y. Sivachenko & Carrie Sougnez & Lihua Zou & Ma, 2012. "Sequence analysis of mutations and translocations across breast cancer subtypes," Nature, Nature, vol. 486(7403), pages 405-409, June.
    5. Philip J. Stephens & Patrick S. Tarpey & Helen Davies & Peter Van Loo & Chris Greenman & David C. Wedge & Serena Nik-Zainal & Sancha Martin & Ignacio Varela & Graham R. Bignell & Lucy R. Yates & Elli , 2012. "The landscape of cancer genes and mutational processes in breast cancer," Nature, Nature, vol. 486(7403), pages 400-404, 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. Zhe Jiang & YoungJun Ju & Amjad Ali & Philip E. D. Chung & Patryk Skowron & Dong-Yu Wang & Mariusz Shrestha & Huiqin Li & Jeff C. Liu & Ioulia Vorobieva & Ronak Ghanbari-Azarnier & Ethel Mwewa & Maria, 2023. "Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Karama Asleh & Gian Luca Negri & Sandra E. Spencer Miko & Shane Colborne & Christopher S. Hughes & Xiu Q. Wang & Dongxia Gao & C. Blake Gilks & Stephen K. L. Chia & Torsten O. Nielsen & Gregg B. Morin, 2022. "Proteomic analysis of archival breast cancer clinical specimens identifies biological subtypes with distinct survival outcomes," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. S. Mouron & M. J. Bueno & A. Lluch & L. Manso & I. Calvo & J. Cortes & J. A. Garcia-Saenz & M. Gil-Gil & N. Martinez-Janez & J. V. Apala & E. Caleiras & Pilar Ximénez-Embún & J. Muñoz & L. Gonzalez-Co, 2022. "Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Peter Eirew & Ciara O’Flanagan & Jerome Ting & Sohrab Salehi & Jazmine Brimhall & Beixi Wang & Justina Biele & Teresa Algara & So Ra Lee & Corey Hoang & Damian Yap & Steven McKinney & Cherie Bates & E, 2022. "Accurate determination of CRISPR-mediated gene fitness in transplantable tumours," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    5. Yang, Xi & Hoadley, Katherine A. & Hannig, Jan & Marron, J.S., 2023. "Jackstraw inference for AJIVE data integration," Computational Statistics & Data Analysis, Elsevier, vol. 180(C).
    6. Manish G & Anil Kumar Badana & Rama Rao Malla, 2017. "Emerging Diagnostic and Prognostic Biomarkers of Triple Negative Breast Cancer," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 1(3), pages 561-565, August.
    7. Jacob Elnaggar & Fern Tsien & Lucio Miele & Chindo Hicks & Clayton Yates & Melisa Davis, 2019. "An Integrative Genomics Approach for Associating Genetic Susceptibility with the Tumor Immune Microenvironment in Triple Negative Breast Cancer," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 15(1), pages 1-12, February.
    8. Egashira, Kento & Yata, Kazuyoshi & Aoshima, Makoto, 2024. "Asymptotic properties of hierarchical clustering in high-dimensional settings," Journal of Multivariate Analysis, Elsevier, vol. 199(C).
    9. María Elena Martínez & Jonathan T Unkart & Li Tao & Candyce H Kroenke & Richard Schwab & Ian Komenaka & Scarlett Lin Gomez, 2017. "Prognostic significance of marital status in breast cancer survival: A population-based study," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-14, May.
    10. Yishai Shimoni, 2018. "Association between expression of random gene sets and survival is evident in multiple cancer types and may be explained by sub-classification," PLOS Computational Biology, Public Library of Science, vol. 14(2), pages 1-15, February.
    11. Anna Dvorkin-Gheva & John A Hassell, 2014. "Identification of a Novel Luminal Molecular Subtype of Breast Cancer," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-10, July.
    12. Marcin Pilarczyk & Mehdi Fazel-Najafabadi & Michal Kouril & Behrouz Shamsaei & Juozas Vasiliauskas & Wen Niu & Naim Mahi & Lixia Zhang & Nicholas A. Clark & Yan Ren & Shana White & Rashid Karim & Huan, 2022. "Connecting omics signatures and revealing biological mechanisms with iLINCS," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    13. Qihuang Zhang & Grace Y. Yi, 2023. "Zero‐inflated Poisson models with measurement error in the response," Biometrics, The International Biometric Society, vol. 79(2), pages 1089-1102, June.
    14. Apostolos Zaravinos & George I Lambrou & Ioannis Boulalas & Dimitris Delakas & Demetrios A Spandidos, 2011. "Identification of Common Differentially Expressed Genes in Urinary Bladder Cancer," PLOS ONE, Public Library of Science, vol. 6(4), pages 1-28, April.
    15. Junhee Seok & Ronald W Davis & Wenzhong Xiao, 2015. "A Hybrid Approach of Gene Sets and Single Genes for the Prediction of Survival Risks with Gene Expression Data," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-15, May.
    16. Qing Qu & Yan Mao & Xiao-chun Fei & Kun-wei Shen, 2013. "The Impact of Androgen Receptor Expression on Breast Cancer Survival: A Retrospective Study and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-1, December.
    17. David Otohinoyi & Aditi Kuchi & Jiande Wu & Chindo Hicks, 2022. "Integrating Genomic Information with Tumor-Immune Microenvironment in Triple-Negative Breast Cancer," IJERPH, MDPI, vol. 19(21), pages 1-20, October.
    18. 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.
    19. Bourret, Pascale & Keating, Peter & Cambrosio, Alberto, 2011. "Regulating diagnosis in post-genomic medicine: Re-aligning clinical judgment?," Social Science & Medicine, Elsevier, vol. 73(6), pages 816-824, September.
    20. G. Gambardella & G. Viscido & B. Tumaini & A. Isacchi & R. Bosotti & D. di Bernardo, 2022. "A single-cell analysis of breast cancer cell lines to study tumour heterogeneity and drug response," Nature Communications, Nature, vol. 13(1), pages 1-12, 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:plo:pone00:0081843. 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: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    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.