大規模なトポロジック変化が結腸癌の悪性進行を抑制する

Sarah E Johnstone¹, Alejandro Reyes², Yifeng Qi³

¹Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02129, USA.

Cell

|August 26, 2020

まとめ

癌はゲノム構造を変えてオープンとクローズドの空間的分割を損ねますこれらのトポロジカルな変化は,抗腫瘍免疫を誘発しながら,幹と侵入を抑制することによって,腫瘍の成長を抑制する可能性があります.

科学分野:

ゲノミクス
癌生物学
エピジェネティクス

背景:

癌は広範囲にわたるDNAメチル化とクロマチンの変化と関連しています.
これらの変化が上位階の染色体構造に与える影響は十分に理解されていません.

研究の目的:

クロマチンループ,トポロジカルに関連したドメイン,大腸腫瘍における大規模なゲノムコンパートメントの変異を特徴付ける.
癌の進行におけるこれらのトポロジ的変化の機能的影響を調査する.

主な方法:

結腸腫瘍と正常結腸のトポロジカルマップの統合
エピジェネティック,トランスクリプション,画像データの分析.
悪性細胞と非悪性細胞におけるゲノム組織の比較

主要な成果:

腫瘍では開いたゲノムと閉じたゲノムを空間的に分ける事が有意に妨げられます.
腫瘍に関連するトポロジカルな変化には,コンパートメント特有の低メチル化およびクロマチンの変化が含まれます.
A/Bコンパートメントのインターフェイスで新しいコンパートメントが再編成され,過剰な分裂を持つ非悪性細胞で同様のシフトが観察されます.

結論:

腫瘍に関連したトポロジカルゲノム変異は,茎性および侵入プログラムを抑制する可能性があります.
これらの変化は抗腫瘍免疫遺伝子を誘発し,悪性腫瘍の進行を抑制する可能性があります.
この発見は,がんにおける表遺伝子学的変化が腫瘍性だけであるという見解に異議を唱える.

キーワード:

DNAメチル化クロマチン大腸がんコンパートメントエピジェネティクスゲノムトポロジー核建築

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