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Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases
BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BMJ Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640139/ https://www.ncbi.nlm.nih.gov/pubmed/29067216 http://dx.doi.org/10.1136/esmoopen-2017-000253 |
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author | Siravegna, Giulia Geuna, Elena Mussolin, Benedetta Crisafulli, Giovanni Bartolini, Alice Galizia, Danilo Casorzo, Laura Sarotto, Ivana Scaltriti, Maurizio Sapino, Anna Bardelli, Alberto Montemurro, Filippo |
author_facet | Siravegna, Giulia Geuna, Elena Mussolin, Benedetta Crisafulli, Giovanni Bartolini, Alice Galizia, Danilo Casorzo, Laura Sarotto, Ivana Scaltriti, Maurizio Sapino, Anna Bardelli, Alberto Montemurro, Filippo |
author_sort | Siravegna, Giulia |
collection | PubMed |
description | BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution. METHODS: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment. RESULTS: Baseline CSF-derived ctDNA analysis revealed TP53 and PIK3CA mutations as well as ERBB2 and cMYC amplification. Post-treatment ctDNA analysis showed decreased markers level in plasma, consistent with extra-CNS disease control, while increased in the CSF, confirming poor treatment benefit in the CNS. DISCUSSION: Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent a useful companion for clinical management of brain metastases. |
format | Online Article Text |
id | pubmed-5640139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-56401392017-10-24 Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases Siravegna, Giulia Geuna, Elena Mussolin, Benedetta Crisafulli, Giovanni Bartolini, Alice Galizia, Danilo Casorzo, Laura Sarotto, Ivana Scaltriti, Maurizio Sapino, Anna Bardelli, Alberto Montemurro, Filippo ESMO Open Original Research BACKGROUND: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution. METHODS: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment. RESULTS: Baseline CSF-derived ctDNA analysis revealed TP53 and PIK3CA mutations as well as ERBB2 and cMYC amplification. Post-treatment ctDNA analysis showed decreased markers level in plasma, consistent with extra-CNS disease control, while increased in the CSF, confirming poor treatment benefit in the CNS. DISCUSSION: Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent a useful companion for clinical management of brain metastases. BMJ Publishing Group 2017-10-09 /pmc/articles/PMC5640139/ /pubmed/29067216 http://dx.doi.org/10.1136/esmoopen-2017-000253 Text en © European Society for Medical Oncology (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Original Research Siravegna, Giulia Geuna, Elena Mussolin, Benedetta Crisafulli, Giovanni Bartolini, Alice Galizia, Danilo Casorzo, Laura Sarotto, Ivana Scaltriti, Maurizio Sapino, Anna Bardelli, Alberto Montemurro, Filippo Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases |
title | Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases |
title_full | Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases |
title_fullStr | Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases |
title_full_unstemmed | Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases |
title_short | Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases |
title_sort | genotyping tumour dna in cerebrospinal fluid and plasma of a her2-positive breast cancer patient with brain metastases |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640139/ https://www.ncbi.nlm.nih.gov/pubmed/29067216 http://dx.doi.org/10.1136/esmoopen-2017-000253 |
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