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

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...

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Autores principales: Krøigård, Anne Bruun, Larsen, Martin Jakob, Lænkholm, Anne-Vibeke, Knoop, Ann S., Jensen, Jeanette D., Bak, Martin, Mollenhauer, Jan, Kruse, Torben A., Thomassen, Mads
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467391/
https://www.ncbi.nlm.nih.gov/pubmed/25730902
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author Krøigård, Anne Bruun
Larsen, Martin Jakob
Lænkholm, Anne-Vibeke
Knoop, Ann S.
Jensen, Jeanette D.
Bak, Martin
Mollenhauer, Jan
Kruse, Torben A.
Thomassen, Mads
author_facet Krøigård, Anne Bruun
Larsen, Martin Jakob
Lænkholm, Anne-Vibeke
Knoop, Ann S.
Jensen, Jeanette D.
Bak, Martin
Mollenhauer, Jan
Kruse, Torben A.
Thomassen, Mads
author_sort Krøigård, Anne Bruun
collection PubMed
description 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.
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spelling pubmed-44673912015-06-22 Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis Krøigård, Anne Bruun Larsen, Martin Jakob Lænkholm, Anne-Vibeke Knoop, Ann S. Jensen, Jeanette D. Bak, Martin Mollenhauer, Jan Kruse, Torben A. Thomassen, Mads Oncotarget Research Paper 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. Impact Journals LLC 2015-01-29 /pmc/articles/PMC4467391/ /pubmed/25730902 Text en Copyright: © 2015 Krøigård et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Krøigård, Anne Bruun
Larsen, Martin Jakob
Lænkholm, Anne-Vibeke
Knoop, Ann S.
Jensen, Jeanette D.
Bak, Martin
Mollenhauer, Jan
Kruse, Torben A.
Thomassen, Mads
Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis
title Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis
title_full Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis
title_fullStr Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis
title_full_unstemmed Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis
title_short Clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis
title_sort clonal expansion and linear genome evolution through breast cancer progression from pre-invasive stages to asynchronous metastasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467391/
https://www.ncbi.nlm.nih.gov/pubmed/25730902
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