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Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors

Identification of driver genes contributes to the understanding of cancer etiology and is imperative for the development of individualized therapies. Gene amplification is a major event in oncogenesis. Driver genes with tumor-specific amplification-dependent overexpression can be therapeutic targets...

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Autores principales: Ohshima, Keiichi, Hatakeyama, Keiichi, Nagashima, Takeshi, Watanabe, Yuko, Kanto, Kaori, Doi, Yuki, Ide, Tomomi, Shimoda, Yuji, Tanabe, Tomoe, Ohnami, Sumiko, Ohnami, Shumpei, Serizawa, Masakuni, Maruyama, Koji, Akiyama, Yasuto, Urakami, Kenichi, Kusuhara, Masatoshi, Mochizuki, Tohru, Yamaguchi, Ken
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428069/
https://www.ncbi.nlm.nih.gov/pubmed/28377632
http://dx.doi.org/10.1038/s41598-017-00219-3
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author Ohshima, Keiichi
Hatakeyama, Keiichi
Nagashima, Takeshi
Watanabe, Yuko
Kanto, Kaori
Doi, Yuki
Ide, Tomomi
Shimoda, Yuji
Tanabe, Tomoe
Ohnami, Sumiko
Ohnami, Shumpei
Serizawa, Masakuni
Maruyama, Koji
Akiyama, Yasuto
Urakami, Kenichi
Kusuhara, Masatoshi
Mochizuki, Tohru
Yamaguchi, Ken
author_facet Ohshima, Keiichi
Hatakeyama, Keiichi
Nagashima, Takeshi
Watanabe, Yuko
Kanto, Kaori
Doi, Yuki
Ide, Tomomi
Shimoda, Yuji
Tanabe, Tomoe
Ohnami, Sumiko
Ohnami, Shumpei
Serizawa, Masakuni
Maruyama, Koji
Akiyama, Yasuto
Urakami, Kenichi
Kusuhara, Masatoshi
Mochizuki, Tohru
Yamaguchi, Ken
author_sort Ohshima, Keiichi
collection PubMed
description Identification of driver genes contributes to the understanding of cancer etiology and is imperative for the development of individualized therapies. Gene amplification is a major event in oncogenesis. Driver genes with tumor-specific amplification-dependent overexpression can be therapeutic targets. In this study, we aimed to identify amplification-dependent driver genes in 1,454 solid tumors, across more than 15 cancer types, by integrative analysis of gene expression and copy number. Amplification-dependent overexpression of 64 known driver oncogenes were found in 587 tumors (40%); genes frequently observed were MYC (25%) and MET (18%) in colorectal cancer; SKP2 (21%) in lung squamous cell carcinoma; HIST1H3B (19%) and MYCN (13%) in liver cancer; KIT (57%) in gastrointestinal stromal tumors; and FOXL2 (12%) in squamous cell carcinoma across tissues. Genomic aberrations in 138 known cancer driver genes and 491 established fusion genes were found in 1,127 tumors (78%). Further analyses of 820 cancer-related genes revealed 16 as potential driver genes, with amplification-dependent overexpression restricted to the remaining 22% of samples (327 tumors) initially undetermined genetic drivers. Among them, AXL, which encodes a receptor tyrosine kinase, was recurrently overexpressed and amplified in sarcomas. Our studies of amplification-dependent overexpression identified potential drug targets in individual tumors.
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spelling pubmed-54280692017-05-15 Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors Ohshima, Keiichi Hatakeyama, Keiichi Nagashima, Takeshi Watanabe, Yuko Kanto, Kaori Doi, Yuki Ide, Tomomi Shimoda, Yuji Tanabe, Tomoe Ohnami, Sumiko Ohnami, Shumpei Serizawa, Masakuni Maruyama, Koji Akiyama, Yasuto Urakami, Kenichi Kusuhara, Masatoshi Mochizuki, Tohru Yamaguchi, Ken Sci Rep Article Identification of driver genes contributes to the understanding of cancer etiology and is imperative for the development of individualized therapies. Gene amplification is a major event in oncogenesis. Driver genes with tumor-specific amplification-dependent overexpression can be therapeutic targets. In this study, we aimed to identify amplification-dependent driver genes in 1,454 solid tumors, across more than 15 cancer types, by integrative analysis of gene expression and copy number. Amplification-dependent overexpression of 64 known driver oncogenes were found in 587 tumors (40%); genes frequently observed were MYC (25%) and MET (18%) in colorectal cancer; SKP2 (21%) in lung squamous cell carcinoma; HIST1H3B (19%) and MYCN (13%) in liver cancer; KIT (57%) in gastrointestinal stromal tumors; and FOXL2 (12%) in squamous cell carcinoma across tissues. Genomic aberrations in 138 known cancer driver genes and 491 established fusion genes were found in 1,127 tumors (78%). Further analyses of 820 cancer-related genes revealed 16 as potential driver genes, with amplification-dependent overexpression restricted to the remaining 22% of samples (327 tumors) initially undetermined genetic drivers. Among them, AXL, which encodes a receptor tyrosine kinase, was recurrently overexpressed and amplified in sarcomas. Our studies of amplification-dependent overexpression identified potential drug targets in individual tumors. Nature Publishing Group UK 2017-04-04 /pmc/articles/PMC5428069/ /pubmed/28377632 http://dx.doi.org/10.1038/s41598-017-00219-3 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ohshima, Keiichi
Hatakeyama, Keiichi
Nagashima, Takeshi
Watanabe, Yuko
Kanto, Kaori
Doi, Yuki
Ide, Tomomi
Shimoda, Yuji
Tanabe, Tomoe
Ohnami, Sumiko
Ohnami, Shumpei
Serizawa, Masakuni
Maruyama, Koji
Akiyama, Yasuto
Urakami, Kenichi
Kusuhara, Masatoshi
Mochizuki, Tohru
Yamaguchi, Ken
Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors
title Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors
title_full Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors
title_fullStr Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors
title_full_unstemmed Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors
title_short Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors
title_sort integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428069/
https://www.ncbi.nlm.nih.gov/pubmed/28377632
http://dx.doi.org/10.1038/s41598-017-00219-3
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