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Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients
BRAF, NRAS and TERT mutations occur in more than 2/3 of melanomas. Its detection in patient’s blood, as circulating tumor DNA (ctDNA), represents a possibility for identification and monitoring of metastatic disease. We proposed to standardize a liquid biopsy platform to identify hotspot mutations i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596487/ https://www.ncbi.nlm.nih.gov/pubmed/33122747 http://dx.doi.org/10.1038/s41598-020-75792-1 |
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author | Marczynski, Gabriella Taques Laus, Ana Carolina dos Reis, Mariana Bisarro Reis, Rui Manuel Vazquez, Vinicius de Lima |
author_facet | Marczynski, Gabriella Taques Laus, Ana Carolina dos Reis, Mariana Bisarro Reis, Rui Manuel Vazquez, Vinicius de Lima |
author_sort | Marczynski, Gabriella Taques |
collection | PubMed |
description | BRAF, NRAS and TERT mutations occur in more than 2/3 of melanomas. Its detection in patient’s blood, as circulating tumor DNA (ctDNA), represents a possibility for identification and monitoring of metastatic disease. We proposed to standardize a liquid biopsy platform to identify hotspot mutations in BRAF, NRAS and TERT in plasma samples from advanced melanoma patients and investigate whether it was associated to clinical outcome. Firstly, we performed digital polymerase chain reaction using tumor cell lines for validation and determination of limit of detection (LOD) of each assay and screened plasma samples from healthy individuals to determine the limit of blank (LOB). Then, we selected 19 stage III and IV patients and determined the somatic mutations status in tumor tissue and track them in patients’ plasma. We established a specific and sensitive methodology with a LOD ranging from 0.13 to 0.37%, and LOB ranging from of 0 to 5.201 copies/reaction. Somatic mutations occurred in 17/19 (89%) patients, of whom seven (41%) had ctDNA detectable their paired plasma. ctDNA detection was associated with shorter progression free survival (p = 0.01). In conclusion, our data support the use of ctDNA as prognosis biomarker, suggesting that patients with detectable levels have an unfavorable outcome. |
format | Online Article Text |
id | pubmed-7596487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75964872020-10-30 Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients Marczynski, Gabriella Taques Laus, Ana Carolina dos Reis, Mariana Bisarro Reis, Rui Manuel Vazquez, Vinicius de Lima Sci Rep Article BRAF, NRAS and TERT mutations occur in more than 2/3 of melanomas. Its detection in patient’s blood, as circulating tumor DNA (ctDNA), represents a possibility for identification and monitoring of metastatic disease. We proposed to standardize a liquid biopsy platform to identify hotspot mutations in BRAF, NRAS and TERT in plasma samples from advanced melanoma patients and investigate whether it was associated to clinical outcome. Firstly, we performed digital polymerase chain reaction using tumor cell lines for validation and determination of limit of detection (LOD) of each assay and screened plasma samples from healthy individuals to determine the limit of blank (LOB). Then, we selected 19 stage III and IV patients and determined the somatic mutations status in tumor tissue and track them in patients’ plasma. We established a specific and sensitive methodology with a LOD ranging from 0.13 to 0.37%, and LOB ranging from of 0 to 5.201 copies/reaction. Somatic mutations occurred in 17/19 (89%) patients, of whom seven (41%) had ctDNA detectable their paired plasma. ctDNA detection was associated with shorter progression free survival (p = 0.01). In conclusion, our data support the use of ctDNA as prognosis biomarker, suggesting that patients with detectable levels have an unfavorable outcome. Nature Publishing Group UK 2020-10-29 /pmc/articles/PMC7596487/ /pubmed/33122747 http://dx.doi.org/10.1038/s41598-020-75792-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Marczynski, Gabriella Taques Laus, Ana Carolina dos Reis, Mariana Bisarro Reis, Rui Manuel Vazquez, Vinicius de Lima Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients |
title | Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients |
title_full | Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients |
title_fullStr | Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients |
title_full_unstemmed | Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients |
title_short | Circulating tumor DNA (ctDNA) detection is associated with shorter progression-free survival in advanced melanoma patients |
title_sort | circulating tumor dna (ctdna) detection is associated with shorter progression-free survival in advanced melanoma patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596487/ https://www.ncbi.nlm.nih.gov/pubmed/33122747 http://dx.doi.org/10.1038/s41598-020-75792-1 |
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