Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer

Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted...

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Veröffentlicht in:Nature communications 2015-11, Vol.6 (1), p.8760, Article 8760
Hauptverfasser: Murtaza, Muhammed, Dawson, Sarah-Jane, Pogrebniak, Katherine, Rueda, Oscar M., Provenzano, Elena, Grant, John, Chin, Suet-Feung, Tsui, Dana W. Y., Marass, Francesco, Gale, Davina, Ali, H. Raza, Shah, Pankti, Contente-Cuomo, Tania, Farahani, Hossein, Shumansky, Karey, Kingsbury, Zoya, Humphray, Sean, Bentley, David, Shah, Sohrab P., Wallis, Matthew, Rosenfeld, Nitzan, Caldas, Carlos
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container_issue 1
container_start_page 8760
container_title Nature communications
container_volume 6
creator Murtaza, Muhammed
Dawson, Sarah-Jane
Pogrebniak, Katherine
Rueda, Oscar M.
Provenzano, Elena
Grant, John
Chin, Suet-Feung
Tsui, Dana W. Y.
Marass, Francesco
Gale, Davina
Ali, H. Raza
Shah, Pankti
Contente-Cuomo, Tania
Farahani, Hossein
Shumansky, Karey
Kingsbury, Zoya
Humphray, Sean
Bentley, David
Shah, Sohrab P.
Wallis, Matthew
Rosenfeld, Nitzan
Caldas, Carlos
description Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution. Individual tumours are heterogeneous with regards to genetic mutations. In this study, the authors use sequencing to follow multiple tumour and plasma samples over 3 years from a breast cancer patient and show mutations detected in the plasma samples could partially reproduce the clonal nature of the primary tumour.
doi_str_mv 10.1038/ncomms9760
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Y.</au><au>Marass, Francesco</au><au>Gale, Davina</au><au>Ali, H. Raza</au><au>Shah, Pankti</au><au>Contente-Cuomo, Tania</au><au>Farahani, Hossein</au><au>Shumansky, Karey</au><au>Kingsbury, Zoya</au><au>Humphray, Sean</au><au>Bentley, David</au><au>Shah, Sohrab P.</au><au>Wallis, Matthew</au><au>Rosenfeld, Nitzan</au><au>Caldas, Carlos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer</atitle><jtitle>Nature communications</jtitle><stitle>Nat Commun</stitle><addtitle>Nat Commun</addtitle><date>2015-11-04</date><risdate>2015</risdate><volume>6</volume><issue>1</issue><spage>8760</spage><pages>8760-</pages><artnum>8760</artnum><issn>2041-1723</issn><eissn>2041-1723</eissn><abstract>Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution. Individual tumours are heterogeneous with regards to genetic mutations. In this study, the authors use sequencing to follow multiple tumour and plasma samples over 3 years from a breast cancer patient and show mutations detected in the plasma samples could partially reproduce the clonal nature of the primary tumour.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26530965</pmid><doi>10.1038/ncomms9760</doi><orcidid>https://orcid.org/0000-0001-7557-2861</orcidid><oa>free_for_read</oa></addata></record>
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subjects 631/67/1347
631/67/68
Adult
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bayes Theorem
Biological evolution
Biopsy
Brain Neoplasms - genetics
Brain Neoplasms - secondary
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer
Carcinoma, Ductal, Breast - drug therapy
Carcinoma, Ductal, Breast - genetics
Carcinoma, Ductal, Breast - metabolism
Carcinoma, Ductal, Breast - pathology
Case-Control Studies
Clonal Evolution - genetics
Deoxycytidine - administration & dosage
Deoxycytidine - analogs & derivatives
Deoxyribonucleic acid
DNA
DNA, Neoplasm - genetics
ErbB-2 protein
Evolution
Female
Gemcitabine
Genomes
Heterogeneity
Humanities and Social Sciences
Humans
Lapatinib
Liver Neoplasms - genetics
Liver Neoplasms - secondary
Lung Neoplasms - genetics
Lung Neoplasms - secondary
Metastases
Metastasis
multidisciplinary
Mutation
Neoplasm Metastasis
Patients
Quinazolines - administration & dosage
Receptor, ErbB-2 - metabolism
Receptors, Estrogen - metabolism
Science
Science (multidisciplinary)
Sequence Analysis, DNA
Spinal Neoplasms - genetics
Spinal Neoplasms - secondary
Tamoxifen - administration & dosage
Trastuzumab - administration & dosage
Tumors
title Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer
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