Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    The clonal and mutational evolution spectrum of primary triple-negative breast cancers

    Access Status
    Fulltext not available
    Authors
    Shah, S.
    Roth, A.
    Goya, R.
    Oloumi, A.
    Ha, G.
    Zhao, Y.
    Turashvili, G.
    Ding, J.
    Tse, K.
    Haffari, G.
    Bashashati, A.
    Prentice, L.
    Khattra, J.
    Burleigh, A.
    Yap, D.
    Bernard, V.
    McPherson, A.
    Shumansky, K.
    Crisan, A.
    Giuliany, R.
    Heravi-Moussavi, A.
    Rosner, J.
    Lai, D.
    Birol, I.
    Varhol, Richard
    Tam, A.
    Dhalla, N.
    Zeng, T.
    Ma, K.
    Chan, S.
    Griffith, M.
    Moradian, A.
    Cheng, S.
    Morin, G.
    Watson, P.
    Gelmon, K.
    Chia, S.
    Chin, S.
    Curtis, C.
    Rueda, O.
    Pharoah, P.
    Damaraju, S.
    MacKey, J.
    Hoon, K.
    Harkins, T.
    Tadigotla, V.
    Sigaroudinia, M.
    Gascard, P.
    Tlsty, T.
    Costello, J.
    Meyer, I.
    Eaves, C.
    Wasserman, W.
    Jones, S.
    Huntsman, D.
    Hirst, M.
    Caldas, C.
    Marra, M.
    Aparicio, S.
    Date
    2012
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Shah, S. and Roth, A. and Goya, R. and Oloumi, A. and Ha, G. and Zhao, Y. and Turashvili, G. et al. 2012. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. 486 (7403): pp. 395-399.
    Source Title
    Nature
    DOI
    10.1038/nature10933
    ISSN
    0028-0836
    School
    Department of Health Policy and Management
    URI
    http://hdl.handle.net/20.500.11937/36670
    Collection
    • Curtin Research Publications
    Abstract

    Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes. © 2012 Macmillan Publishers Limited. All rights reserved.

    Related items

    Showing items related by title, author, creator and subject.

    • Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
      Shah, S.; Morin, R.; Khattra, J.; Prentice, L.; Pugh, T.; Burleigh, A.; Delaney, A.; Gelmon, K.; Guliany, R.; Senz, J.; Steidl, C.; Holt, R.; Jones, S.; Sun, M.; Leung, G.; Moore, R.; Severson, T.; Taylor, G.; Teschendorff, A.; Tse, K.; Turashvili, G.; Varhol, Richard; Warren, R.; Watson, P.; Zhao, Y.; Caldas, C.; Huntsman, D.; Hirst, M.; Marra, M.; Aparicio, S. (2009)
      Recent advances in next generation sequencing have made it possible to precisely characterize all somatic coding mutations that occur during the development and progression of individual cancers. Here we used these ...
    • Complete genomic landscape of a recurring sporadic parathyroid carcinoma
      Kasaian, K.; Wiseman, S.; Thiessen, N.; Mungall, K.; Corbett, R.; Qian, J.; Nip, K.; He, A.; Tse, K.; Chuah, E.; Varhol, Richard; Pandoh, P.; McDonald, H.; Zeng, T.; Tam, A.; Schein, J.; Birol, I.; Mungall, A.; Moore, R.; Zhao, Y.; Hirst, M.; Marra, M.; Walker, B.; Jones, S. (2013)
      Parathyroid carcinoma is a rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level, and the deleterious ...
    • Concurrent CIC mutations, IDH mutations, and 1p/19q loss distinguish oligodendrogliomas from other cancers
      Yip, S.; Butterfield, Y.; Morozova, O.; Chittaranjan, S.; Blough, M.; An, J.; Birol, I.; Chesnelong, C.; Chiu, R.; Chuah, E.; Corbett, R.; Docking, R.; Firme, M.; Hirst, M.; Jackman, S.; Karsan, A.; Li, H.; Louis, D.; Maslova, A.; Moore, R.; Moradian, A.; Mungall, K.; Perizzolo, M.; Qian, J.; Roldan, G.; Smith, E.; Tamura-Wells, J.; Thiessen, N.; Varhol, Richard; Weiss, S.; Wu, W.; Young, S.; Zhao, Y.; Mungall, A.; Jones, S.; Morin, G.; Chan, J.; Cairncross, J.; Marra, M. (2012)
      Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.