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Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors

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Title: Novel putative drivers revealed by targeted exome sequencing of advanced solid tumors
Authors: Pannuti, A
Filipovic, A
Hicks, C
Lefkowitz, E
Ptacek, T
Stebbing, J
Miele, L
Item Type: Journal Article
Abstract: 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.
Issue Date: 23-Mar-2018
Date of Acceptance: 10-Mar-2018
URI: http://hdl.handle.net/10044/1/58392
DOI: https://dx.doi.org/10.1371/journal.pone.0194790
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS ONE
Volume: 13
Issue: 3
Copyright Statement: © 2018 Pannuti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: National Institute for Health Research
Funder's Grant Number: NIHR-RP-011-053
Keywords: MD Multidisciplinary
General Science & Technology
Publication Status: Published
Conference Place: United States
Article Number: e0194790
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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