2013 Fiscal Year Final Research Report
Comprehensive Analysis for Improvement of the Therapeutic Outcome against Esophageal Cancer by the High-Precision Molecular and Genetic Evaluation
| Project/Area Number |
21229015
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (S)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
MORI Masaki 大阪大学, 医学(系)研究科(研究院), 教授 (70190999)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJITA Hiromasa 久留米大学, 医学部外科学講座, 教授 (20129638)
SUZUKI Sadao 名古屋市立大学, 医学部医学系研究科公衆衛生学, 教授 (20226509)
YAMAMOTO Ken 九州大学, 生体防御医学研究所, 准教授 (60274528)
NATSUGOE Syouji 鹿児島大学, 大学院・医歯学総合研究科 先進治療科学専攻 腫瘍学講座, 教授 (70237577)
KAJIYAMA Yoshiaki 順天堂大学, 医学部消化器外科学講座, 教授 (70241239)
|
|---|
| Project Period (FY) |
2009-05-11 – 2014-03-31
|
| Keywords | 食道扁平上皮癌 / エキソーム解析 / CYP2A6 / ALDH2 / pathway解析 / コピー数解析 |
|---|
| Research Abstract |
To obtain a landscape of genomic alterations in ESCC, we performed whole-exome sequencing on 144 paired DNA samples from Japanese cohort, combined with SNP-array based CN profiling. Substitution patterns of single-nucleotide mutations substantially vary among cases, and the variation was significantly associated with not only alcohol and tobacco consumption, but also related genetic factors: ALDH2 and CYP2A6 polymorphisms. We also identified TP53, NOTCH1, MLL2, NFE2L2, etc. as significantly mutated genes. Moreover, TET2 and NFE2L2 mutations contribute to the malignancy by upregulating invasiveness and oxidoreductase activity, respectively. Finally, our pathway-level analysis shows that genomic alteration are dispersed across cancer-associated pathways including cell cycle, epigenetic regulators, NOTCH, RTK-PI3K pathways etc. Collectively, this study contributes to understanding of ESCC pathophysiology and provides a new basis for designing novel therapeutic strategies.
|
