前駆病変に着目した卵巣明細胞腺癌研究

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Author: 前田, 大地ほか

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Publication date: 2013-02-18

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Note (General)：: 金沢大学医薬保健研究域医学系 / 東京大学近年の網羅的遺伝子解析によって明細胞腺癌の約半数にARID1A遺伝子の変異が認められることが明らかになった。ARID1Aは卵巣明細胞腺癌の発生に関わる主要な遺伝子と考えられ、その変異は前駆病変の段階から存在すると想定される。本研究で我々は、ARID1A遺伝子...

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Material Type: 文書・図像類
Title: 前駆病変に着目した卵巣明細胞腺癌研究
Author/Editor: 前田, 大地
Maeda, Daichi
Author Heading: 前田, 大地
Maeda, Daichi
Publication Date: 2013-02-18
Publication Date (W3CDTF): 2013-02-18
Alternative Title: Investigation of the development of ovarian clear cell adenocarcinoma with emphasis on its precursor
Periodical title: 平成23(2011)年度科学研究費補助金研究活動スタート支援研究成果報告書 = 2011 Fiscal Year Final Research Report
No. or year of volume/issue: 2010 – 2011
Volume: 2010 – 2011
Pages: 5p.-
Text Language Code: jpn
Subject Heading: 卵巣
明細胞腺癌
ARID1A
Human pathology
Target Audience: 一般
Note (General): 金沢大学医薬保健研究域医学系 / 東京大学
近年の網羅的遺伝子解析によって明細胞腺癌の約半数にARID1A遺伝子の変異が認められることが明らかになった。ARID1Aは卵巣明細胞腺癌の発生に関わる主要な遺伝子と考えられ、その変異は前駆病変の段階から存在すると想定される。本研究で我々は、ARID1A遺伝子の変異がARID1A蛋白の発現消失につながることを突き止め、免疫組織化学的手法で明細胞腺癌の中からARID1A変異群を選び出すことに成功した。さらに、明細胞腺癌をARID1A変異群と非変異群に分けて臨床病理学的な比較検討を行い、両群の組織像に有意な違いがないこと、変異群において腹膜播種の頻度が高いもののoverall survivalに差がないことを示した。これらの結果は、ARID1Aが明細胞腺癌のprogressionやbehaviorよりもむしろtumor initiationに関与していることを示唆するものである。
Recent genome-wide analysis has demonstrated that somatic mutations in ARID1A are the most common molecular genetic changes in ovarian clear cell adenocarcinoma (CCA). ARID1A mutations which occurred in approximately half of CCA cases. In this study, we first correlated ARID1A mutation status and ARID1A immunoreactivity then applied immunohistochemistry to determine if there is any clinicopathological features associated with the loss of ARID1A expression in a total of 149 CCA cases. We demonstrated that loss of ARID1A expression was associated with ARID1A inactivating mutations in CCA (p= 0.0073). ARID1A immunoreactivity was undetectable or very week in 88 (59%) of 149 CCAs. There was no statistically significant difference of ARID1A negative and positive cases in terms of histopathological features (structural patterns and nuclear atypia), age, clinical sage, overall survival, and frequency of lymph node metastasis. However, we observed that loss of ARID1A expression correlated with lower chance of peritoneal dissemination (p<0.05). In conclusion, this study provides the first analysis of ARID1A mutations and clinicopathological features and we demonstrate that mutations in ARID1A resulted in loss of ARID1A protein expression in ovarian carcinomas and there was no significant difference of ARID1A positive and negative cases in all the clinical parameters examined except for frequency of peritoneal dissemination.
研究課題/領域番号:22890036, 研究期間(年度):2010 - 2011
出典：研究課題「前駆病変に着目した卵巣明細胞腺癌研究」課題番号22890036（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-22890036/22890036seika/）を加工して作成
DOI: 10.24517/00061997
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=30585500
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-22890036/
https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-22890036/22890036seika/
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