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Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?

BACKGROUND: Cancer is first and foremost a disease of the genome. Specific genetic signatures within a tumour are prognostic of disease outcome, reflect subclonal architecture and intratumour heterogeneity, inform treatment choices and predict the emergence of resistance to targeted therapies. Minim...

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Autores principales: Clifford, Harry W., Cassidy, Amy P., Vaughn, Courtney, Tsai, Evaline S., Seres, Bianka, Patel, Nirmesh, O’Neill, Hannah L., Hewage, Emil, Cassidy, John W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Vienna 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119837/
https://www.ncbi.nlm.nih.gov/pubmed/27933110
http://dx.doi.org/10.1186/s12645-016-0023-8
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author Clifford, Harry W.
Cassidy, Amy P.
Vaughn, Courtney
Tsai, Evaline S.
Seres, Bianka
Patel, Nirmesh
O’Neill, Hannah L.
Hewage, Emil
Cassidy, John W.
author_facet Clifford, Harry W.
Cassidy, Amy P.
Vaughn, Courtney
Tsai, Evaline S.
Seres, Bianka
Patel, Nirmesh
O’Neill, Hannah L.
Hewage, Emil
Cassidy, John W.
author_sort Clifford, Harry W.
collection PubMed
description BACKGROUND: Cancer is first and foremost a disease of the genome. Specific genetic signatures within a tumour are prognostic of disease outcome, reflect subclonal architecture and intratumour heterogeneity, inform treatment choices and predict the emergence of resistance to targeted therapies. Minimally invasive liquid biopsies can give temporal resolution to a tumour’s genetic profile and allow the monitoring of treatment response through levels of circulating tumour DNA (ctDNA). However, the detection of ctDNA in repeated liquid biopsies is currently limited by economic and time constraints associated with targeted sequencing. METHODS: Here we bioinformatically profile the mutational and copy number spectrum of The Cancer Genome Network’s lung adenocarcinoma dataset to uncover recurrently mutated genomic loci. RESULTS: We build a panel of 400 hotspot mutations and show that the coverage extends to more than 80% of the dataset at a median depth of 8 mutations per patient. Additionally, we uncover several novel single-nucleotide variants present in more than 5% of patients, often in genes not commonly associated with lung adenocarcinoma. CONCLUSION: With further optimisation, this hotspot panel could allow molecular diagnostics laboratories to build curated primer banks for ‘off-the-shelf’ monitoring of ctDNA by droplet-based digital PCR or similar techniques, in a time- and cost-effective manner.
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spelling pubmed-51198372016-12-06 Profiling lung adenocarcinoma by liquid biopsy: can one size fit all? Clifford, Harry W. Cassidy, Amy P. Vaughn, Courtney Tsai, Evaline S. Seres, Bianka Patel, Nirmesh O’Neill, Hannah L. Hewage, Emil Cassidy, John W. Cancer Nanotechnol Research BACKGROUND: Cancer is first and foremost a disease of the genome. Specific genetic signatures within a tumour are prognostic of disease outcome, reflect subclonal architecture and intratumour heterogeneity, inform treatment choices and predict the emergence of resistance to targeted therapies. Minimally invasive liquid biopsies can give temporal resolution to a tumour’s genetic profile and allow the monitoring of treatment response through levels of circulating tumour DNA (ctDNA). However, the detection of ctDNA in repeated liquid biopsies is currently limited by economic and time constraints associated with targeted sequencing. METHODS: Here we bioinformatically profile the mutational and copy number spectrum of The Cancer Genome Network’s lung adenocarcinoma dataset to uncover recurrently mutated genomic loci. RESULTS: We build a panel of 400 hotspot mutations and show that the coverage extends to more than 80% of the dataset at a median depth of 8 mutations per patient. Additionally, we uncover several novel single-nucleotide variants present in more than 5% of patients, often in genes not commonly associated with lung adenocarcinoma. CONCLUSION: With further optimisation, this hotspot panel could allow molecular diagnostics laboratories to build curated primer banks for ‘off-the-shelf’ monitoring of ctDNA by droplet-based digital PCR or similar techniques, in a time- and cost-effective manner. Springer Vienna 2016-11-22 2016 /pmc/articles/PMC5119837/ /pubmed/27933110 http://dx.doi.org/10.1186/s12645-016-0023-8 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research
Clifford, Harry W.
Cassidy, Amy P.
Vaughn, Courtney
Tsai, Evaline S.
Seres, Bianka
Patel, Nirmesh
O’Neill, Hannah L.
Hewage, Emil
Cassidy, John W.
Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?
title Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?
title_full Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?
title_fullStr Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?
title_full_unstemmed Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?
title_short Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?
title_sort profiling lung adenocarcinoma by liquid biopsy: can one size fit all?
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119837/
https://www.ncbi.nlm.nih.gov/pubmed/27933110
http://dx.doi.org/10.1186/s12645-016-0023-8
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