2001 Fiscal Year Annual Research Report

遺伝子診断の導入による新しい乳癌診療体系の確立

Research Project

Project/Area Number	11307019
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)	丹治芳郎大阪大学, 医学系研究科, 助手 (90263269) 田口哲也大阪大学, 医学系研究科, 講師 (80243260) 玉木康博大阪大学, 医学系研究科, 助教授 (10273690) 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 / 家族性乳癌 / 化学療法感受性 / 遺伝子発現プロファイル
Research Abstract	遺伝子診断の乳癌診療への応用を目指して研究を進めている。以下に、現在までの研究成果を要約する。(1)家族性乳癌の遺伝子診断:家族性乳癌113家系中、BRCA1の変異を15家系、BRCA2の変異を21家系に同定した。Haplotype解析によって、日本人に特有なfounder mutation(BRCA1,codon63,TTA to TAA(nonsense); BRCA2,4bp(5802-5805)deletion)を同定した。(2)乳癌の易罹患性の診断:CYP17のpromoter領域に存在するSNP、CYP19のexon2のSNPとintron4のTTTA repeat、および、ER-αのpromoter領域に存在するTArepeat(n=13)が乳癌の罹患リスクと相関することが示唆された。(3)予後診断:17番染色体の数的異常(monosomy)、および、BRCA2 mRNA、wt-1 mRNA、steroid sulfatase mRNAの発現は、それぞれ古典的な予後因子(腫瘍径・リンパ節転移、組織学的異型度等、ER)とは独立した予後因子であった。また、約2,500個の遺伝子発現をATAC-PCR法で測定した結果、cluster解析によって乳癌を3群に分類することができた。この3群は、生物学的特徴(ホルモン依存性、組織学的悪性度、予後等)を異にすることが分かった。(4)乳癌の化学療法感受性の診断:Tc99m-MIBIシンチグラフィー、および、collagen gel droplet embedded culture-drog sensitivity test(CD-DST)が化学療法感受性の診断に有用であること、更には、docetaxel(DOC)を不活化するCYP3A4の乳癌組織内での発現がDOC耐性の指標として有用であることが示唆された。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] Miyoshi, Y., et al.: "Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers"Int J Cancer. 92. 370-373 (2001)
[Publications] Tsukamoto, F., et al.: "Clinicopathological analysis of breast cancers with chromosomal aneusomy detected by fluorescence In situ hybridization"Cancer. 93. 165-170 (2001)
[Publications] Motomura, K., et al.: "Combination techinique is superior to dye alone in identification of the sentinel dode in breast cancer patients"J Surg Oncol. 76. 96-99 (2001)
[Publications] Egawa, C., et al.: "Quantitative analysis of BRCA1 and BRCA2 mRNA expression in sporadic breast carcinomas and its relationship with clinicopathological characleristics"Jpn J Cancer Res. 92・6. 624-630 (2001)
[Publications] Egawa, C., et al.: "Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancers"Int J Cancer. 95・4. 255-259 (2001)
[Publications] Takamura, Y., et al.: "Prediction of chemotherapeutic response by technetium-99m-MIBI scintigraphy in breast cancer patients"Cancer. 92・2. 232-239 (2001)
[Publications] Motomura, K., et al.: "Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients"Eur J Surg Onco. 27・2. 141-145 (2001)
[Publications] Takami, S., et al.: "Chromosomal instability detected by fluorescen in situ hybridization in Japanese breast cancer patients"Clin Chim Acta. 308. 127-131 (2001)
[Publications] Iwao, K., et al.: "Quantitative analysis of estrogen receptor-alpha and-beta messenger RNA expression in human pancreatic cancers by real-time polymerase chain reaction"Cancer Lett. 170・1. 91-97 (2001)
[Publications] Ooka, M., et al.: "Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer"Breast Cancer Res Treat. 67・2. 169-175 (2001)
[Publications] Miyoshi, Y., et al.: "Clinicopathological characteristics of estrogen receptor-beta positive human breast cancers"Jpn J Cancer Res. 92. 1057-1061 (2001)
[Publications] Miyoshi, Y., et al.: "Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer"Int J Cancer. 97. 129-132 (2001)
[Publications] Egawa, C., et al.: "Quantitative Analysis of Estrogen Receptor-alpha and-beta Messenger RNA Expression in Normal and Malignant Thyroid Tissues by Real-time Polymerase Chain Reaction"Oncology. 61. 293-298 (2001)
[Publications] Miyoshi, Y., et al.: "Involvement of 17beta-Hydroxysteroid dehydrogenase up-regulation in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers"Int J Cancer. 94. 685-689 (2001)
[Publications] Takamura, Y., et al.: "Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in hnman breast cancers"Int J Cancer. (in press).
[Publications] Egawa, C., et al.: "High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients"Int J Cancer. (in press).
[Publications] Shimazu, K., et al.: "Comparison between periareolar and peritumora Injection of radiotracer forsentinel lymph node biopsy in breast cancer patients"Surgery. (in press).
[Publications] Miyoshi, Y., et al.: "Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women"Breast Journal. (in press).
[Publications] Miyoshi, Y., et al.: "Acceleration of chromosomal instability of BRCA1-associated hereditery breast cancers by p53 abnormality"Breast Journal. (in press).

2001 Fiscal Year Annual Research Report

遺伝子診断の導入による新しい乳癌診療体系の確立

Principal Investigator

野口 眞三郎 大阪大学, 医学系研究科, 教授 (10303942)

Research Products

[Publications] Miyoshi, Y., et al.: "Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers"Int J Cancer. 92. 370-373 (2001)

[Publications] Tsukamoto, F., et al.: "Clinicopathological analysis of breast cancers with chromosomal aneusomy detected by fluorescence In situ hybridization"Cancer. 93. 165-170 (2001)

[Publications] Motomura, K., et al.: "Combination techinique is superior to dye alone in identification of the sentinel dode in breast cancer patients"J Surg Oncol. 76. 96-99 (2001)

[Publications] Egawa, C., et al.: "Quantitative analysis of BRCA1 and BRCA2 mRNA expression in sporadic breast carcinomas and its relationship with clinicopathological characleristics"Jpn J Cancer Res. 92・6. 624-630 (2001)

[Publications] Egawa, C., et al.: "Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancers"Int J Cancer. 95・4. 255-259 (2001)

[Publications] Takamura, Y., et al.: "Prediction of chemotherapeutic response by technetium-99m-MIBI scintigraphy in breast cancer patients"Cancer. 92・2. 232-239 (2001)

[Publications] Motomura, K., et al.: "Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients"Eur J Surg Onco. 27・2. 141-145 (2001)

[Publications] Takami, S., et al.: "Chromosomal instability detected by fluorescen in situ hybridization in Japanese breast cancer patients"Clin Chim Acta. 308. 127-131 (2001)

[Publications] Iwao, K., et al.: "Quantitative analysis of estrogen receptor-alpha and-beta messenger RNA expression in human pancreatic cancers by real-time polymerase chain reaction"Cancer Lett. 170・1. 91-97 (2001)

[Publications] Ooka, M., et al.: "Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer"Breast Cancer Res Treat. 67・2. 169-175 (2001)

[Publications] Miyoshi, Y., et al.: "Clinicopathological characteristics of estrogen receptor-beta positive human breast cancers"Jpn J Cancer Res. 92. 1057-1061 (2001)

[Publications] Miyoshi, Y., et al.: "Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer"Int J Cancer. 97. 129-132 (2001)

[Publications] Egawa, C., et al.: "Quantitative Analysis of Estrogen Receptor-alpha and-beta Messenger RNA Expression in Normal and Malignant Thyroid Tissues by Real-time Polymerase Chain Reaction"Oncology. 61. 293-298 (2001)

[Publications] Miyoshi, Y., et al.: "Involvement of 17beta-Hydroxysteroid dehydrogenase up-regulation in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers"Int J Cancer. 94. 685-689 (2001)

[Publications] Takamura, Y., et al.: "Prediction of chemotherapeutic response by collagen gel droplet embedded culture-drug sensitivity test in hnman breast cancers"Int J Cancer. (in press).

[Publications] Egawa, C., et al.: "High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients"Int J Cancer. (in press).

[Publications] Shimazu, K., et al.: "Comparison between periareolar and peritumora Injection of radiotracer forsentinel lymph node biopsy in breast cancer patients"Surgery. (in press).

[Publications] Miyoshi, Y., et al.: "Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women"Breast Journal. (in press).

[Publications] Miyoshi, Y., et al.: "Acceleration of chromosomal instability of BRCA1-associated hereditery breast cancers by p53 abnormality"Breast Journal. (in press).

野口眞三郎大阪大学, 医学系研究科, 教授 (10303942)