膵液中の癌関連遺伝子異常を指標とした膵癌の早期診断に関する研究

• Material Type: 文書・図像類
• Title: 膵液中の癌関連遺伝子異常を指標とした膵癌の早期診断に関する研究
• Author/Editor: 澤武, 紀雄; Sawabu, Norio
• Author Heading: 澤武, 紀雄; Sawabu, Norio
• Publication, Distribution, etc.: 金沢大学がん研究所
• Publication Date: 2005-05
• Publication Date (W3CDTF): 2005-05
• Alternative Title: Analysis of Tumor-Related Genes In Pancreatic Juice Aiming to be Useful for Early Diagnosis of Pancreatic Cancer
• Periodical title: 平成16(2004)年度 科学研究費補助金 基盤研究(B) 研究成果報告書 = 2004 Fiscal Year Final Research Report
• No. or year of volume/issue: 2002-2004
• Volume: 2002-2004
• Pages: 13p.-
• Text Language Code: jpn
• Subject Heading: 膵液; 膵癌; 膵管内乳頭粘液性腫瘍(IPMN); p53; メチル化; mesothelin; h-TERT; SARP-2; pancreatic juice; pancreatic cancer; intraductal papillary mucinous neoplasm (IPMN); hypermethylation
• Target Audience: 一般
• Note (General): ERCP下に採取した膵液とPTCなどで採取した胆汁において沈渣のみでなく上清からDNAを抽出して、p53分析を行い、その膵癌(PCa)診断における有用性を検討した。Pca患者におけるp53変異の陽性率は膵液上清で43%(9/21)であるのに対し、沈渣では29%(6/21)であり、いずれかでの陽性率は57%(12/12)に達した。一方、慢性膵炎(CP)25例では総て陰性であった。また、膵液細胞診陰性の膵癌でも47%(7/15)にp53変異が陽性であった。さらに、胆道癌患者におけるp53変異は胆汁上清で50%(15/30)、沈渣で33%(10/30)に検出されたが、胆石症20例では総て陰性であった。膵液、胆汁いずれでもp53変異の検出率は沈渣よりも上清で高く、p53変異の癌特異性は非常に優れていた。膵液中mesothein mRNAの発現を検討するとPCaで52%(11/21)、膵管内乳頭粘液性腫瘍(IPMN)で45%(5/11)、CPで14%(3/22)に陽性であり、PCaでCPに比して有意に高率であった。h-TERT mRNAの高感度な定量的測定法を開発し、血清と膵液で測定したが、良性疾患でもリンパ球由来のかTERTが検出され、癌特異性は高くなかった。膵液中各種癌関連遺伝子のメチル化を検討すると、pp ENKのメチル化はPCaで50%(14/28)、IPMNで27%(4/15)、CPで5%(1/20)に認められ、PCaでCPに比して有意に高率であった。SARP2のメチル化はPCaで74%(24/35)、IPMNで94%(15/16)、CPで11%(2/19)でPCaやIPMNではCPに比して明らかに高率であった。さらに、NPTX2のメチル化はPCaで77%(24/35)、IPMNで63%(10/16)、CPで46%(6/13)であり、PCaでCPに比して有意に高率であった。これら遺伝子のメチル化の検出率をIPMNの良・悪性群で比較しても明らかな差異はなく、これらの癌関連遺伝子のメチル化はPCaの発癌過程におけるearly eventであると推察され、現在、定量的測定により癌特異性を向上させようとしている。; We analyzed mutations of p53 in DNA extract not only from the sediment(Sed) but also from the supernatant(sup) of aspirated pancreatic juice(PJ) by ERCP and bile obtained by PTC or ERBD. The incidence of p53 mutations was 43%(9 of 21) and 29%(6 of 21) in the Sup and the Sed of PJ from patients with pancreatic cancer(PCa), respectively, and nurse to 52%(11 of 21) in the combination assay with Sup and Sed. Moreover, p53 mutations were detected in 47%(7 of 15) of PCa cases in which the cyto logic diagnosis was negative. Among 25 patients with chronic pancreatitis(CP), none harbored mutant p53. In bile abtained from patients with biliary tract cancer, the positive rate of p53 mutations was 50%(15 of 30) in the Sup and 33%(10 of 30) in the Sed. On the other hand, there were no pantients with cholelithiasis harboring mutant p53. These results could indicate that the incidence of p53 mutation was higher in the Sup than in the Sed, and the specificity of p53 mutation was higher in the Sup than in the Sed, and the specificity of p53 mutation for cancer was very high. Mesothlin mRNA expression in the PJ was discovered in 11(52%) of 21 patients with PCa,5(45%) of 11 with intraductal papillary mucinous neoplasm(IPMN) and 3(14%) of 22 with CP. There was significant difference between PCa and CP for mesothelin mRNA. We developed an highly sensitive quantitative analysis for h-TERT mRNA using real-time RT-PCR and measured the amount of h-TERT mRNA in serum and PJ. The levels of h-TERT mRNA were elevated in almost all cases with PCa but also in considerable cases with benign lesions, suggesting low specificity of h-TERT mRNA for cancer. h-TERT mRNA in body fluids from benign lesions originates from lymphocyte.Using methylation-specific PCR, we nextly analyzed the methylation status of 3 CpG islands of ppENK, SARP2 and NPTX2 in PJ samples. Aberrant methylation of ppENK in the PJ was detected in 14(50%) of 28 patients with PCa, 4(27%) of 15 with IPMN and 1(15%) of 20 with CP, and that of NPTX2 was detected in 24(77%) of 35 patients with PCa, 10(63%) of 16 with IPMN and 6(43%) of 13 with CP. The incidence of aberrant methylation of ppENK or NPTX2 was significantly higher in PCa than in CP. Furthermore, we found aberrant methylation of SARP2 in PJ in 24(74%) of 35 patients with PCa, 15(94%) of 16 with IPMN and 2(11%) of 19 with CP. The incidence of aberrant methylation of SARP2 was significantly higher in PCa or IPMN than in CP. Although the prevalence of aberrant methylation of the tumor-related genes in PJ from PCa was strikingly high, its specificity for cancer was not sufficient. There was no significant difference between benign and malignant groups of IPMN, suggesting that aberrant menthylation of these genes is a early event in PCa development, and quantitative detection of aberrant methylation in PJ may have potential diagnostic implication for PCa.; 研究課題/領域番号:14370177, 研究期間(年度):2002-2004; 出典：「膵液中の癌関連遺伝子異常を指標とした膵癌の早期診断に関する研究」研究成果報告書 課題番号14370177 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）) 本文データは著者版報告書より作成
• DOI: 10.24517/00049342
• Access Restrictions: 限定公開
• Related Material: https://kaken.nii.ac.jp/search/?qm=90019969; https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14370177/; https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-14370177/143701772004kenkyu_seika_hokoku_gaiyo/
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA