Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors
Abstract 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 therapeuti...
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Nature Portfolio
2017
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oai:doaj.org-article:e4035a2588bc4f009de6291a94d531c32021-12-02T11:40:52ZIntegrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors10.1038/s41598-017-00219-32045-2322https://doaj.org/article/e4035a2588bc4f009de6291a94d531c32017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00219-3https://doaj.org/toc/2045-2322Abstract 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.Keiichi OhshimaKeiichi HatakeyamaTakeshi NagashimaYuko WatanabeKaori KantoYuki DoiTomomi IdeYuji ShimodaTomoe TanabeSumiko OhnamiShumpei OhnamiMasakuni SerizawaKoji MaruyamaYasuto AkiyamaKenichi UrakamiMasatoshi KusuharaTohru MochizukiKen YamaguchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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DOAJ |
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DOAJ |
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Medicine R Science Q |
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Medicine R Science Q Keiichi Ohshima Keiichi Hatakeyama Takeshi Nagashima Yuko Watanabe Kaori Kanto Yuki Doi Tomomi Ide Yuji Shimoda Tomoe Tanabe Sumiko Ohnami Shumpei Ohnami Masakuni Serizawa Koji Maruyama Yasuto Akiyama Kenichi Urakami Masatoshi Kusuhara Tohru Mochizuki Ken Yamaguchi Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors |
| description |
Abstract 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. |
| format |
article |
| author |
Keiichi Ohshima Keiichi Hatakeyama Takeshi Nagashima Yuko Watanabe Kaori Kanto Yuki Doi Tomomi Ide Yuji Shimoda Tomoe Tanabe Sumiko Ohnami Shumpei Ohnami Masakuni Serizawa Koji Maruyama Yasuto Akiyama Kenichi Urakami Masatoshi Kusuhara Tohru Mochizuki Ken Yamaguchi |
| author_facet |
Keiichi Ohshima Keiichi Hatakeyama Takeshi Nagashima Yuko Watanabe Kaori Kanto Yuki Doi Tomomi Ide Yuji Shimoda Tomoe Tanabe Sumiko Ohnami Shumpei Ohnami Masakuni Serizawa Koji Maruyama Yasuto Akiyama Kenichi Urakami Masatoshi Kusuhara Tohru Mochizuki Ken Yamaguchi |
| author_sort |
Keiichi Ohshima |
| title |
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_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_sort |
integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/e4035a2588bc4f009de6291a94d531c3 |
| work_keys_str_mv |
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| _version_ |
1718395553287503872 |