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 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..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
|---|---|
| Enthalten in: |
Scientific Reports - 7(2017), 1, Seite 13 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Keiichi Ohshima [VerfasserIn] |
|---|
| Links: |
doi.org [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1038/s41598-017-00219-3 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
DOAJ052538346 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ052538346 | ||
| 003 | DE-627 | ||
| 005 | 20230503143945.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230227s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41598-017-00219-3 |2 doi | |
| 035 | |a (DE-627)DOAJ052538346 | ||
| 035 | |a (DE-599)DOAJe4035a2588bc4f009de6291a94d531c3 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 0 | |a Keiichi Ohshima |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Integrated analysis of gene expression and copy number identified potential cancer driver genes with amplification-dependent overexpression in 1,454 solid tumors |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a 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. | ||
| 653 | 0 | |a Medicine | |
| 653 | 0 | |a R | |
| 653 | 0 | |a Science | |
| 653 | 0 | |a Q | |
| 700 | 0 | |a Keiichi Hatakeyama |e verfasserin |4 aut | |
| 700 | 0 | |a Takeshi Nagashima |e verfasserin |4 aut | |
| 700 | 0 | |a Yuko Watanabe |e verfasserin |4 aut | |
| 700 | 0 | |a Kaori Kanto |e verfasserin |4 aut | |
| 700 | 0 | |a Yuki Doi |e verfasserin |4 aut | |
| 700 | 0 | |a Tomomi Ide |e verfasserin |4 aut | |
| 700 | 0 | |a Yuji Shimoda |e verfasserin |4 aut | |
| 700 | 0 | |a Tomoe Tanabe |e verfasserin |4 aut | |
| 700 | 0 | |a Sumiko Ohnami |e verfasserin |4 aut | |
| 700 | 0 | |a Shumpei Ohnami |e verfasserin |4 aut | |
| 700 | 0 | |a Masakuni Serizawa |e verfasserin |4 aut | |
| 700 | 0 | |a Koji Maruyama |e verfasserin |4 aut | |
| 700 | 0 | |a Yasuto Akiyama |e verfasserin |4 aut | |
| 700 | 0 | |a Kenichi Urakami |e verfasserin |4 aut | |
| 700 | 0 | |a Masatoshi Kusuhara |e verfasserin |4 aut | |
| 700 | 0 | |a Tohru Mochizuki |e verfasserin |4 aut | |
| 700 | 0 | |a Ken Yamaguchi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Scientific Reports |d Nature Portfolio, 2011 |g 7(2017), 1, Seite 13 |w (DE-627)DOAJ000049077 |x 20452322 |7 nnns |
| 773 | 1 | 8 | |g volume:7 |g year:2017 |g number:1 |g pages:13 |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41598-017-00219-3 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/e4035a2588bc4f009de6291a94d531c3 |z kostenfrei |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41598-017-00219-3 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/2045-2322 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |d 7 |j 2017 |e 1 |h 13 | ||