頭頸部領域における悪性腫瘍のゲノム構造異常の解析と標的遺伝子の同定

头颈部恶性肿瘤基因组结构异常分析及靶基因鉴定

• 批准号: 16791009
• 负责人: 四ノ宮 隆
• 金额: $ 2.18万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16791009/
• 关键词: 頭頸部悪性腫瘍; ゲノム構造異常

頭頸部悪性腫瘍の発症にかかわるゲノム構造異常を解明するために,我々がこれまで頭頸部扁平上皮癌に行ってきたCGH法による染色体のコピー数の変化の解析およびFISH法で検出した染色体の数的異常の解析のデータの蓄積をさらに進め,頭頸部領域での発生母地別の比較検討を行った.さらに前癌病変についても解析を行い,発癌における時間的な変化の過程を追求した.比較検討の結果から,染色体コピー数の増加を示す遺伝子増幅領域,または染色体コピー数の減少を示す遺伝子欠失領域に存在する頭頸部悪性腫瘍の発症にかかわる可能性を持つ標的遺伝子候補を同定し,さらにそれらの標的遺伝子についてDNAメチル化,クロマチン構造の変化,転写調節因子などのエピジェネティックな要因との関連を検討するために,methylation specific PCR法を用いたDNAのメチル化の検索を行った.すでに頭頸部悪性腫瘍においてもm-RNAレベルでの発現変化を検出し,胃癌や大腸癌などの共通欠失領域である1p36に含まれるRUNX-3や,肺癌等で発現の変化が報告されており,喫煙と関連が示唆されるMGMT,腫瘍の転移に関連するDAP-Kなどいくつかの標的遺伝子についても同様にメチル化の検索を行い、それぞれの遺伝子のメチル化を検出した.得られたデータから頭頸部悪性腫瘍の術前診断,予後診断への応用の可能性を検討する.本研究で捕らえた染色体遺伝子の構造異常とデータベース化した臨床経過(リンパ節転移,遠隔転移の有無,抗ガン剤耐性,重複癌など)とを比較し,診断,治療に有益な情報を得られるか否かの検討をさらにすすめる.

The analysis of chromosome number variation by CGH and the analysis of chromosome number accumulation by FISH in squamous cell carcinoma of the head and neck were carried out. In the process of cancer development, the process of cancer development and transformation is pursued. Comparison of the results of the study, the increase in the number of chromosomes indicates that there is an increase in the number of chromosomes, the decrease in the number of chromosomes indicates that there is an increase in the number of chromosomes, the decrease in the number of chromosomes, the decrease in the number of chromosomes indicates that there is an increase in the number of chromosomes, the increase in the number of chromosomes, the decrease in the number of chromosomes indicates that there is an increase in the number of chromosomes, the increase in the number of chromosomes, the decrease in the number of chromosomes, the number of chromosomes, the decrease in the number of chromosomes, the number of chromosomes, the decrease DNA methylation specific PCR method was used to detect the expression of regulatory factors. The development of m-RNA in head and neck cancer was detected in the common missing area of gastric cancer and colorectal cancer, including RUNX-3, lung cancer, etc. The development of m-RNA in head and neck cancer was reported in the common missing area of gastric cancer and colorectal cancer, including RUNX-3, lung cancer, etc. The development of m-RNA in head and neck cancer was detected in the common missing area of gastric cancer and colorectal cancer. It's not like we're going to be able to do anything about it. Preoperative diagnosis of head and neck swelling was obtained, and the possibility of post-operative diagnosis was discussed. This study aims to detect structural abnormalities in chromosomal DNA and to compare clinical findings (such as nodal shift, distant shift, resistance to cancer, and duplication of cancer) with diagnostic and therapeutic information.