乳がんの遺伝子診断とその臨床応用

• 研究課題/領域番号: 12217075
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 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: 玉木 康博 大阪大学, 医学系研究科, 助教授 (10273690) ; 三好 康雄 大阪大学, 医学系研究科, 助手 (50283784) ; 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)
• 研究期間 (年度): 2000 – 2004
• 研究課題ステータス: 完了 (2004年度)
• 配分額: 53,300千円 (直接経費: 53,300千円); 2004年度: 10,700千円 (直接経費: 10,700千円); 2003年度: 9,600千円 (直接経費: 9,600千円); 2002年度: 9,500千円 (直接経費: 9,500千円); 2001年度: 9,500千円 (直接経費: 9,500千円); 2000年度: 14,000千円 (直接経費: 14,000千円)
• キーワード: 乳がん / 遺伝子発現プロファイル / ATAC-PCR / 予後 / 化学療法感受性 / 乳癌 / 遺伝子診断 / 易罹患性 / 微小転移 / 遺伝性乳癌 / 白血病 / WT1 mRNA

研究概要

乳癌治療においては、ホルモン療法と化学療法が汎用されるが、最大の問題点はそれらの治療効果を予測し得る正確な指標が存在しないことである。そこで、我々は、ATAC(adaptor tagged competitive)-PCR法による乳癌組織の遺伝子発現プロファイル解析を用いて、新しい乳癌のホルモン療法および化学療法の効果予測法を開発すべく本研究を実施した。(1)ホルモン療法感受性の診断:原発乳癌301例を対象として2500遺伝子の発現プロファイルをATAC-PCR法で解析し、ERと有意に相関する21遺伝子を同定した。乳癌術後に補助ホルモン療法を受けた患者を対象としてこれらの遺伝子発現がホルモン療法感受性の指標として有用であるかどうかを検討したところ、STC2とalpha-1-antichymotrypsinの遺伝子発現が高値の乳癌は、低値の乳癌に比して有意に予後が良好であることが判明した。このことは、この2つの遺伝子の発現がホルモン療法感受性予測因子として有用であることを示唆している。(2)化学療法感受性の診断:術前化学療法施行予定の乳癌症例を対象として、まず、遺伝子診断用の腫瘍サンプルを採取し、その後に化学療法(docetaxel)を実施した。Docetaxel療法施行前に採取した腫瘍組織(n=47例)における遺伝子発現プロファイル(2412遺伝子)をATAC-PCR法で解析し、化学療法有効例と無効例における遺伝子発現プロファイルの差異から、化学療法効果予測因子の抽出およびそれに基づく効果予測診断を試みた。効果予測の診断能をcross-validation法で検討した結果、その正診率は96%(45/47例)と非常に高率であった。更に、別の23例を用いてprospectiveに効果予測を行った結果、その正診率も78%(18/23例)と良好であった。

研究成果

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