Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis

Research output: Contribution to journalJournal articleResearchpeer-review

  • Anne Bruun Krøigård
  • Martin Jakob Larsen
  • Lænkholm, Anne-Vibeke
  • Ann S Knoop
  • Jeanette D Jensen
  • Martin Bak
  • Jan Mollenhauer
  • Torben A Kruse
  • Mads Thomassen

Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence.

Original languageEnglish
JournalOncoTarget
Volume6
Issue number8
Pages (from-to)5634-49
Number of pages16
ISSN1949-2553
DOIs
Publication statusPublished - 2015

    Research areas

  • Breast Neoplasms, DNA Copy Number Variations, Disease Progression, Epidemiologic Methods, Female, Genome, Humans, Linear Models, Neoplasm Metastasis, Neoplasm Staging, Journal Article, Research Support, Non-U.S. Gov't

ID: 179317493