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Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors
Next generation sequencing (NGS) is becoming increasingly integrated into oncological practice and clinical research. NGS methods have also provided evidence for clonal evolution of cancers during disease progression and treatment. The number of variants associated with response to specific therapeu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865730/ https://www.ncbi.nlm.nih.gov/pubmed/29570743 http://dx.doi.org/10.1371/journal.pone.0194790 |
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author | Pannuti, Antonio Filipovic, Aleksandra Hicks, Chindo Lefkowitz, Elliot Ptacek, Travis Stebbing, Justin Miele, Lucio |
author_facet | Pannuti, Antonio Filipovic, Aleksandra Hicks, Chindo Lefkowitz, Elliot Ptacek, Travis Stebbing, Justin Miele, Lucio |
author_sort | Pannuti, Antonio |
collection | PubMed |
description | Next generation sequencing (NGS) is becoming increasingly integrated into oncological practice and clinical research. NGS methods have also provided evidence for clonal evolution of cancers during disease progression and treatment. The number of variants associated with response to specific therapeutic agents keeps increasing. However, the identification of novel driver mutations as opposed to passenger (phenotypically silent or clinically irrelevant) mutations remains a major challenge. We conducted targeted exome sequencing of advanced solid tumors from 44 pre-treated patients with solid tumors including breast, colorectal and lung carcinomas, neuroendocrine tumors, sarcomas and others. We catalogued established driver mutations and putative new drivers as predicted by two distinct algorithms. The established drivers we detected were consistent with published observations. However, we also detected a significant number of mutations with driver potential never described before in each tumor type we studied. These putative drivers belong to key cell fate regulatory networks, including potentially druggable pathways. Should our observations be confirmed, they would support the hypothesis that new driver mutations are selected by treatment in clinically aggressive tumors, and indicate a need for longitudinal genomic testing of solid tumors to inform second line cancer treatment. |
format | Online Article Text |
id | pubmed-5865730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58657302018-03-28 Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors Pannuti, Antonio Filipovic, Aleksandra Hicks, Chindo Lefkowitz, Elliot Ptacek, Travis Stebbing, Justin Miele, Lucio PLoS One Research Article Next generation sequencing (NGS) is becoming increasingly integrated into oncological practice and clinical research. NGS methods have also provided evidence for clonal evolution of cancers during disease progression and treatment. The number of variants associated with response to specific therapeutic agents keeps increasing. However, the identification of novel driver mutations as opposed to passenger (phenotypically silent or clinically irrelevant) mutations remains a major challenge. We conducted targeted exome sequencing of advanced solid tumors from 44 pre-treated patients with solid tumors including breast, colorectal and lung carcinomas, neuroendocrine tumors, sarcomas and others. We catalogued established driver mutations and putative new drivers as predicted by two distinct algorithms. The established drivers we detected were consistent with published observations. However, we also detected a significant number of mutations with driver potential never described before in each tumor type we studied. These putative drivers belong to key cell fate regulatory networks, including potentially druggable pathways. Should our observations be confirmed, they would support the hypothesis that new driver mutations are selected by treatment in clinically aggressive tumors, and indicate a need for longitudinal genomic testing of solid tumors to inform second line cancer treatment. Public Library of Science 2018-03-23 /pmc/articles/PMC5865730/ /pubmed/29570743 http://dx.doi.org/10.1371/journal.pone.0194790 Text en © 2018 Pannuti et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Pannuti, Antonio Filipovic, Aleksandra Hicks, Chindo Lefkowitz, Elliot Ptacek, Travis Stebbing, Justin Miele, Lucio Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors |
title | Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors |
title_full | Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors |
title_fullStr | Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors |
title_full_unstemmed | Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors |
title_short | Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors |
title_sort | novel putative drivers revealed by targeted exome sequencing of advanced solid tumors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865730/ https://www.ncbi.nlm.nih.gov/pubmed/29570743 http://dx.doi.org/10.1371/journal.pone.0194790 |
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