2001 年度実績報告書

遺伝子診断の導入による新しい乳癌診療体系の確立

研究課題

研究課題/領域番号	11307019
研究機関	大阪大学
研究代表者	野口眞三郎大阪大学, 医学系研究科, 教授 (10303942)
研究分担者	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)
キーワード	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
研究概要	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。

研究成果

(19件)

すべてその他

すべて文献書誌 (19件)

[文献書誌] 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)
[文献書誌] Tsukamoto, F., et al.: "Clinicopathological analysis of breast cancers with chromosomal aneusomy detected by fluorescence In situ hybridization"Cancer. 93. 165-170 (2001)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Takamura, Y., et al.: "Prediction of chemotherapeutic response by technetium-99m-MIBI scintigraphy in breast cancer patients"Cancer. 92・2. 232-239 (2001)
[文献書誌] 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)
[文献書誌] Takami, S., et al.: "Chromosomal instability detected by fluorescen in situ hybridization in Japanese breast cancer patients"Clin Chim Acta. 308. 127-131 (2001)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] Miyoshi, Y., et al.: "Clinicopathological characteristics of estrogen receptor-beta positive human breast cancers"Jpn J Cancer Res. 92. 1057-1061 (2001)
[文献書誌] Miyoshi, Y., et al.: "Prediction of response to docetaxel by CYP3A4 mRNA expression in breast cancer"Int J Cancer. 97. 129-132 (2001)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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).
[文献書誌] Egawa, C., et al.: "High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients"Int J Cancer. (in press).
[文献書誌] Shimazu, K., et al.: "Comparison between periareolar and peritumora Injection of radiotracer forsentinel lymph node biopsy in breast cancer patients"Surgery. (in press).
[文献書誌] Miyoshi, Y., et al.: "Breast cancer risk associated with CYP1A1 genetic polymorphisms in Japanese women"Breast Journal. (in press).
[文献書誌] Miyoshi, Y., et al.: "Acceleration of chromosomal instability of BRCA1-associated hereditery breast cancers by p53 abnormality"Breast Journal. (in press).

2001 年度 実績報告書

遺伝子診断の導入による新しい乳癌診療体系の確立

研究代表者

野口 眞三郎 大阪大学, 医学系研究科, 教授 (10303942)

研究成果

[文献書誌] 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)

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

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

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

[文献書誌] 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)

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

[文献書誌] 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)

[文献書誌] 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)

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

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

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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).

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

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

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

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

2001 年度実績報告書

野口眞三郎大阪大学, 医学系研究科, 教授 (10303942)