論文 - 詳細
| RRC ID | 6592 |
|---|---|
| 著者 | Kubo T, Kuroda Y, Shimizu H, Kokubu A, Okada N, Hosoda F, Arai Y, Nakamura Y, Taniguchi H, Yanagihara K, Imoto I, Inazawa J, Hirohashi S, Shibata T. |
| タイトル | Resequencing and copy number analysis of the human tyrosine kinase gene family in poorly differentiated gastric cancer. |
| ジャーナル | Carcinogenesis |
| Abstract |
The tyrosine kinase (TK) family is an important regulator of signaling pathways that control a variety of physiological and pathological conditions, and a substantial proportion of TK genes are genetically altered in cancer. To clarify the somatic mutation profile of TK genes and discover potential targets for gastric cancer (GC) therapy, we undertook a systematic screening of mutations in the kinase domains of all human TK genes (636 exons of 90 genes) in 17 GC cell lines and 52 microdissected primary GCs with poorly differentiated histology. We identified 26 non-synonymous alterations (22 genes in total) that included 11 sequence alterations in cell lines and 15 somatic mutations in primary tumors. Recurrent mutations were found in four genes including a known oncogene (NTRK3), the Src kinase family (LTK and CSK) and a potential Wnt signal activator (ROR2). In addition, we analyzed copy number alterations of all the TK gene loci in the same cohort samples by array-based comparative genomic hybridization analysis and identified 24 high-level amplifications and two homozygous deletions. Both sequence alteration and frequent copy number aberration were detected in two TK genes (HCK and ERBB2), strongly suggesting that they encode potential oncogenes in GC. Our focused and integrated analyses of systemic resequencing and gene copy number have revealed the novel onco-kinome profile of GC and pave the way to a comprehensive understanding of the GC genome. |
| 巻・号 | 30(11) |
| ページ | 1857-64 |
| 公開日 | 2009-11-1 |
| DOI | 10.1093/carcin/bgp206 |
| PII | bgp206 |
| PMID | 19734198 |
| MeSH | Cell Line, Tumor Exons Gene Dosage Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Genes, Neoplasm Humans Mutation* Protein-Tyrosine Kinases / genetics* Receptor Protein-Tyrosine Kinases / genetics Receptor Tyrosine Kinase-like Orphan Receptors / genetics Receptor, trkC / genetics Sequence Analysis Stomach Neoplasms / enzymology Stomach Neoplasms / genetics* Stomach Neoplasms / pathology src-Family Kinases / genetics |
| IF | 4.603 |
| 引用数 | 34 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | |