Abstract
Gastric cancer (GC) is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs. Recent studies using nextgeneration sequencing (NGS) have revealed a number of potential cancer-driving genes in GC. Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4, a member of the cadherin gene family. Mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) have been found in 47% of GCs. Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC. Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery, such as DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs and microRNAs. Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings. The antihuman epidermal growth receptor 2 (HER2) antibody trastuzumab has led to an era of personalized therapy in GC. In addition, ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor (VEGFR)-2, is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy. Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets, as well as useful biomarkers. In this review, we will summarize the recent advances in the understanding of the molecular pathogenesis of GC, focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.
| Original language | English |
|---|---|
| Pages (from-to) | 3927-3937 |
| Number of pages | 11 |
| Journal | World Journal of Gastroenterology |
| Volume | 20 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - 2014 |
| Externally published | Yes |
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Keywords
- Epigenetic field defect
- Gastric washes
- Insulin-like growth factor 1 receptor
- MicroRNA
- Microsatellite instability
- Next-generation sequencing
ASJC Scopus subject areas
- Gastroenterology
- Medicine(all)
Cite this
An updated review of gastric cancer in the next-generation sequencing era : Insights from bench to bedside and vice versa. / Yamamoto, Hiroyuki; Watanabe, Yoshiyuki; Maehata, Tadateru; Morita, Ryo; Yoshida, Yoshihito; Oikawa, Ritsuko; Ishigooka, Shinya; Ozawa, Shun Ichiro; Matsuo, Yasumasa; Hosoya, Kosuke; Yamashita, Masaki; Taniguchi, Hiroaki; Nosho, Katsuhiko; Suzuki, Hiromu; Yasuda, Hiroshi; Shinomura, Yasuhisa; Itoh, Fumio.
In: World Journal of Gastroenterology, Vol. 20, No. 14, 2014, p. 3927-3937.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An updated review of gastric cancer in the next-generation sequencing era
T2 - Insights from bench to bedside and vice versa
AU - Yamamoto, Hiroyuki
AU - Watanabe, Yoshiyuki
AU - Maehata, Tadateru
AU - Morita, Ryo
AU - Yoshida, Yoshihito
AU - Oikawa, Ritsuko
AU - Ishigooka, Shinya
AU - Ozawa, Shun Ichiro
AU - Matsuo, Yasumasa
AU - Hosoya, Kosuke
AU - Yamashita, Masaki
AU - Taniguchi, Hiroaki
AU - Nosho, Katsuhiko
AU - Suzuki, Hiromu
AU - Yasuda, Hiroshi
AU - Shinomura, Yasuhisa
AU - Itoh, Fumio
PY - 2014
Y1 - 2014
N2 - Gastric cancer (GC) is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs. Recent studies using nextgeneration sequencing (NGS) have revealed a number of potential cancer-driving genes in GC. Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4, a member of the cadherin gene family. Mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) have been found in 47% of GCs. Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC. Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery, such as DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs and microRNAs. Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings. The antihuman epidermal growth receptor 2 (HER2) antibody trastuzumab has led to an era of personalized therapy in GC. In addition, ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor (VEGFR)-2, is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy. Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets, as well as useful biomarkers. In this review, we will summarize the recent advances in the understanding of the molecular pathogenesis of GC, focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.
AB - Gastric cancer (GC) is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs. Recent studies using nextgeneration sequencing (NGS) have revealed a number of potential cancer-driving genes in GC. Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4, a member of the cadherin gene family. Mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) have been found in 47% of GCs. Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC. Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery, such as DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs and microRNAs. Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings. The antihuman epidermal growth receptor 2 (HER2) antibody trastuzumab has led to an era of personalized therapy in GC. In addition, ramucirumab, a monoclonal antibody targeting vascular endothelial growth factor receptor (VEGFR)-2, is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy. Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets, as well as useful biomarkers. In this review, we will summarize the recent advances in the understanding of the molecular pathogenesis of GC, focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.
KW - Epigenetic field defect
KW - Gastric washes
KW - Insulin-like growth factor 1 receptor
KW - MicroRNA
KW - Microsatellite instability
KW - Next-generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=84898413155&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898413155&partnerID=8YFLogxK
U2 - 10.3748/wjg.v20.i14.3927
DO - 10.3748/wjg.v20.i14.3927
M3 - Article
C2 - 24744582
AN - SCOPUS:84898413155
VL - 20
SP - 3927
EP - 3937
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
SN - 1007-9327
IS - 14
ER -