脳脊髄液の液体生検による瘤の進化の追跡
Alexandra M Miller1, Ronak H Shah2,3,4, Elena I Pentsova1
1Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|January 25, 2019
まとめ
脳脊髄液 (CSF) での腫瘍DNAを検出することは,拡散性グリオマの遺伝子型を決定するより侵襲的な方法を提供します. この方法は,患者のほぼ半数の遺伝子変異を特定し,疾患の進行を理解し,標的治療を導くのに役立ちました.
科学分野:
- 神経腫瘍学
- 分子診断
- ゲノミクス
背景:
- 拡散性膠原腫は成人における一般的な脳腫瘍であり,治療には遺伝子プロファイリングが必要です.
- 現在の組織生検は侵入的であり,繰り返す必要があるかもしれません.
- 血液中の循環する腫瘍DNA (ctDNA) の検出は困難ですが,CSFの分析は有望です.
研究 の 目的:
- 脳脊髄液 (CSF) でのグリオマ特有のDNAを検出する可能性を評価する.
- CSFのゲノムプロファイルと腫瘍生検を比較する.
- 脊髄液のctDNAと疾患負担と患者のアウトカムとの関連を評価する.
主な方法:
- 脊椎骨髄液のサンプルを85人の患者に腰椎穴穴で採取した.
- 次世代のシーケンシングは,CSFの腫瘍由来DNAを分析するために使用されました.
- CSFのゲノム変異は,既存の腫瘍生検データと比較した.
主要な成果:
- 腫瘍に由来するDNAは,患者の49. 4% (42/85) のCSFで検出されました.
- CSFで検出されたグリオマのゲノムは 腫瘍生検のゲノムとほぼ一致しました
- 初期の遺伝的変異 (例えば,1p/19q codeletion,IDH1/2変異) は一貫して発見され,信号伝達経路は進化を示した.
結論:
- CSFのctDNA分析は,グリオマの遺伝子型決定のための実行可能な,最小侵襲的方法である.
- このアプローチは 初期の遺伝的特徴を明らかにし ゲノム進化を追跡できます
- 脊髄液経由での膠原体ゲノムのモニタリングは,遺伝子型指向の治療法の開発を支援することができます.
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