DICER1変異は,卵巣セルトリ・レーディグ細胞腫瘍を伴う,または含まない家族性多胞性臓で発生する
Thomas Rio Frio1, Amin Bahubeshi, Chryssa Kanellopoulou
1Program in Cancer Genetics, Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada.
JAMA
|January 6, 2011
まとめ
ゲルムラインのDICER1変異は,多胞性多胞性 (MNG) と関連するセルトーリ-レイディグ細胞腫瘍 (SLCT) に関連しており,多胞性肺芽細胞腫とは無関係です. これらの変異は,マイクロRNA発現パターンを破壊する.
科学分野:
- 遺伝学 遺伝学とは
- 腫瘍学 腫瘍学
- エンドクリノロジー エンドクリノロジー
背景:
- 毒性のない多節性 (MNG) は一般的ですが,その遺伝的根拠は十分に理解されていません.
- 家族性MNG症例は,時には卵巣セルトリ・レーディグ細胞腫瘍 (SLCT) と同時に発生する.
- ゲルムラインのDICER1変異は,多発性肺芽細胞腫 (PPB),MNG,および性腺腫瘍に関与しています.
研究 の 目的:
- PPBが存在しない場合,ファミリアルMNG (SLCT付きまたはなし) とDICER1変異の関連性を調査する.
- DICER1の突然変異が,家族性MNGとSLCTの遺伝的感受性に寄与するかどうかを判断する.
主な方法:
- 5つの家族から53人の個人をスクリーニングし (2MNG,3MNG/SLCT) DICER1変異を検出した.
- 血液リンパ球と腫瘍組織を分析し,DICER1変異,ヘテロジゴシティの喪失,遺伝子発現,およびマイクロRNA (miRNA) 失調を検出しました.
主要な成果:
- 5つのファミリーにわたる37人の個体で,遺伝子のDICER1変異を特定しました.
- タンパク質の断片化,インフレームの削除,ミッセンスの変異を含む様々な変異タイプを特徴づけた.
- DICER1変異媒体のmiRNAの乱れが観察され,遺伝子調節に対する下流効果を示しています.
結論:
- DICER1変異は,PPBに関係なく,家族的なMNGとSLCTを持つMNGに関連しています.
- ゲルムラインのDICER1変異は,影響を受けた個体におけるmiRNA発現パターンの失調につながる.
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