2000 Fiscal Year Annual Research Report

乳がん・白血病の遺伝子診断とその臨床応用

Research Project

Project/Area Number	12217075
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (C)
Research Institution	Osaka University
Principal Investigator	野口眞三郎大阪大学, 医学系研究科, 教授 (10303942)
Co-Investigator(Kenkyū-buntansha)	田口哲也大阪大学, 医学系研究科, 講師 (80243260) 芝英一大阪大学, 医学系研究科, 助教授 (90215997) 杉山治夫大阪大学, 医学系研究科, 教授 (70162906) 塚本文音大阪大学, 医学系研究科, 助手 (70303964) 三好康雄大阪大学, 医学系研究科, 助手 (50283784)
Keywords	乳癌 / 遺伝子診断 / 微小転移 / 遺伝性乳癌 / 白血病 / WT1 mRNA
Research Abstract	[乳癌](1)FISHによる乳癌の鑑別診断:穿刺細胞診検体(n=176)を用いたFISH法(1、11、17番染色体の数的異常の検出)による乳腺腫瘍の良悪性の鑑別診断法は、通常の細胞診(86.4%)と同等の正診率(91.5%で)を有し、かつ、細胞診では悪性と判定し得なかった乳癌15中13例がFISH法では悪性と診断し得た。また、chromosomal instability(CIN)とリンパ節転移が相関をすることを明らかにした。(2)Cytokeratin(CK)19mRNA RT-PCRによる微小骨髄転移の診断:CK19mRNAをターゲットとした定量的RT-PCR(Taq-Man法)によって検出される骨髄微小転移が乳癌の独立した予後因子であることを明らかとした。(3)家族性乳癌の遺伝子診断:乳癌家系(n=113)の発端者より採血してBRCA1およびBRCA2を解析した結果、BRCA1の変異が15家系、BRCA2の変異が21家系に同定された。卵巣癌患者が存在する家系。第一度近親者に三人以上乳癌患者が存在する家系、両側性乳癌患者が存在する家系、若年発症患者(40歳以下)が存在する家系ではBRCA1またはBRCA2に変異を有する頻度がそれぞれ58.3%、36%,40%、38%と高率であった。 [白血病]同種骨髄移植(BMT)後の微小残存病変(Minimal Residual Disease=MRD)の動態を、WT1mRNA発現量の定量(WT1assay)でフォローした。BMT前の骨髄でのWT1mRNA発現量は、AML、ALLで、102(コピー/μgRNA)レベルであり、CMLで103(コピー/μgRNA)レベルであった。またBMT前の末梢血でのWT1mRNA発現量は、AML、ALLで10(コピー/μgRNA)レベルであり、CMLで、102(コピー/μgRNA)レベルであった。BMT後1ヵ月目の骨髄での、WT1mRNA発現量はAML、ALL、CMLとも102(コピー/μgRNA)程度であり、BMT1ヵ月後、AMLでは、約1logの減少、ALLでは、著変なく、CMLでは約2logの減少が見られた。BMT後の再発率と、BMT前のWT1mRNAレベル及びBMT1ヵ月後のWT1mRNAレベルとの間の相関を解析したところ、BMT前のWT1mRNAレベルのみが、再発率と相関を示し、BMT後1ヵ月目のWT1mRNAレベルと再発率との間には相関が見られなかった。よって、BMT前のWT1mRNA量が、BMT後の予後を決定することが明らかになった。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Iwao,K., et al.: "Quantitative Analysis of Estrogen Receptor-b Messenger RNA and its Variants in Human Breast Cancers."Int J Cancer,. (in press). (2000)
[Publications] Iwao,K., et al.: "Quantitative Analysis of Estrogen Receptor-a and -b Messenger RNA Expression in Human Breast Cancers by Real-time Polymerase Chain Reaction."Cancer,. (in press). (2000)
[Publications] Miyoshi,Y., et al.: "Genetic Polymorphism in CYP17 and Breast Cancer Risk in Japanese Women."Eur J Cancer,. (in press). (2000)
[Publications] Miyoshi,Y., et al.: "Association of Centrosomal Kinase STK15/BTAK mRNA Expression with Chromosomal Instability in Human Breast Cancers."Int J Cancer,. (in press). (2000)
[Publications] Tsukamoto,F., et al.: "Clinicopathological Analysis of Breast Cancers with Chromosomal Aneusomy Detected by Fluorescence In Situ Hybridization."Cancer Cytopathol,. (in press). (2000)
[Publications] Miyoshi,Y., et al.: "Acceleration of Chromosomal Instability of BRCA1-Associated Hereditary Breast Cancers by p53 Abnormality."Breast Journal,. (in press). (2000)
[Publications] Miyoshi,Y., et al.: "Breast Cancer Risk Associated with Polymorphism in CYP19 in Japanese Women."Int J Cancer. 84・9. 325-328 (2000)
[Publications] Miyoshi,Y., et al.: "Acceleration of Chromosomal Instability by Loss of BRCA1 Expression and p53 Abnormality in Sporadic Breast Cancers."Cancer Lett. 159・2. 211-216 (2000)
[Publications] Tsukamoto,F., et al.: "Detection of Chromosomal Aneusomy by Fluorescence In Situ Hybridization in Fine Needle Aspirates from Breast Tumors : Application to Preoperative Diagnosis of Cancer."Cancer Cytopathol,. (in press). (2000)
[Publications] Ikeda,N., et al.: "Prognostic Significance of Occult Bone Marrow Micrometastases of Breast Cancer Detected by Quantitative Polymerase Chain Reaction for Cytokeratin 19 mRNA.."Jpn J Cancer Res. 91. 918-924 (2000)
[Publications] Ikeda,N., et al.: "Frequency of BRCA1 and BRCA2 Germline Mutations in Japanese Breast Cancer Families."Int J Cancer,. (in press). (2000)
[Publications] Kim,SJ., et al.: "Detection of Breast Cancer Micrometastases in Peripheral Blood Using Immunomagnetic separation and immunocytochemistry."Breast Cancer,. (in press). (2000)
[Publications] Tsuboi,A., et al.: "Cytotoxic T-lymphocyte responses elicited to Wilms' tumor gene WT1 product by DNA vaccination."J Clin Immunol. 20. 195-202 (2000)
[Publications] Kakugawa,K., et al.: "Efficient induction of peptide-specific cytotoxic T lymphocytes by LPS-activated spleen cells."Microbiol Immunol. 44. 123-133 (2000)
[Publications] Oka,Y., et al.: "Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms' tumor gene (WT1) product."Immunogenetics. 51. 99-107 (2000)
[Publications] Oka,Y., et al.: "Cancer immunotherapy targeting Wilms' tumor gene WT1 product."J Immunol. 164. 1873-1880 (2000)

2000 Fiscal Year Annual Research Report

乳がん・白血病の遺伝子診断とその臨床応用

Principal Investigator

野口 眞三郎 大阪大学, 医学系研究科, 教授 (10303942)

Research Products

[Publications] Iwao,K., et al.: "Quantitative Analysis of Estrogen Receptor-b Messenger RNA and its Variants in Human Breast Cancers."Int J Cancer,. (in press). (2000)

[Publications] Iwao,K., et al.: "Quantitative Analysis of Estrogen Receptor-a and -b Messenger RNA Expression in Human Breast Cancers by Real-time Polymerase Chain Reaction."Cancer,. (in press). (2000)

[Publications] Miyoshi,Y., et al.: "Genetic Polymorphism in CYP17 and Breast Cancer Risk in Japanese Women."Eur J Cancer,. (in press). (2000)

[Publications] Miyoshi,Y., et al.: "Association of Centrosomal Kinase STK15/BTAK mRNA Expression with Chromosomal Instability in Human Breast Cancers."Int J Cancer,. (in press). (2000)

[Publications] Tsukamoto,F., et al.: "Clinicopathological Analysis of Breast Cancers with Chromosomal Aneusomy Detected by Fluorescence In Situ Hybridization."Cancer Cytopathol,. (in press). (2000)

[Publications] Miyoshi,Y., et al.: "Acceleration of Chromosomal Instability of BRCA1-Associated Hereditary Breast Cancers by p53 Abnormality."Breast Journal,. (in press). (2000)

[Publications] Miyoshi,Y., et al.: "Breast Cancer Risk Associated with Polymorphism in CYP19 in Japanese Women."Int J Cancer. 84・9. 325-328 (2000)

[Publications] Miyoshi,Y., et al.: "Acceleration of Chromosomal Instability by Loss of BRCA1 Expression and p53 Abnormality in Sporadic Breast Cancers."Cancer Lett. 159・2. 211-216 (2000)

[Publications] Tsukamoto,F., et al.: "Detection of Chromosomal Aneusomy by Fluorescence In Situ Hybridization in Fine Needle Aspirates from Breast Tumors : Application to Preoperative Diagnosis of Cancer."Cancer Cytopathol,. (in press). (2000)

[Publications] Ikeda,N., et al.: "Prognostic Significance of Occult Bone Marrow Micrometastases of Breast Cancer Detected by Quantitative Polymerase Chain Reaction for Cytokeratin 19 mRNA.."Jpn J Cancer Res. 91. 918-924 (2000)

[Publications] Ikeda,N., et al.: "Frequency of BRCA1 and BRCA2 Germline Mutations in Japanese Breast Cancer Families."Int J Cancer,. (in press). (2000)

[Publications] Kim,SJ., et al.: "Detection of Breast Cancer Micrometastases in Peripheral Blood Using Immunomagnetic separation and immunocytochemistry."Breast Cancer,. (in press). (2000)

[Publications] Tsuboi,A., et al.: "Cytotoxic T-lymphocyte responses elicited to Wilms' tumor gene WT1 product by DNA vaccination."J Clin Immunol. 20. 195-202 (2000)

[Publications] Kakugawa,K., et al.: "Efficient induction of peptide-specific cytotoxic T lymphocytes by LPS-activated spleen cells."Microbiol Immunol. 44. 123-133 (2000)

[Publications] Oka,Y., et al.: "Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms' tumor gene (WT1) product."Immunogenetics. 51. 99-107 (2000)

[Publications] Oka,Y., et al.: "Cancer immunotherapy targeting Wilms' tumor gene WT1 product."J Immunol. 164. 1873-1880 (2000)

野口眞三郎大阪大学, 医学系研究科, 教授 (10303942)