エンハンサーハイジャックにより,髄膜芽細胞腫におけるGFI1ファミリーの腫瘍遺伝子が活性化されます

Paul A Northcott¹, Catherine Lee², Thomas Zichner³

¹1] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany [2].

Nature

|July 22, 2014

まとめ

ゲノム解析により,攻撃的な小児脳腫瘍,第3および第4群の髄芽細胞腫の新たな要因が明らかになりました. 構造的変異は,強化器ハイジャックを通じてGFI1およびGFI1B腫瘍遺伝子を活性化します.

科学分野:

腫瘍学腫瘍学
遺伝学遺伝学とは
小児医学は,小児科の医学である.

背景:

メドゥルブロブラストーマは,治療に重大な毒性を持つ悪性小児脳腫瘍です.
ゲノム研究により,4つの分子サブグループが特定され,グループ3と4が最も一般的です.
グループ3と4の髄芽細胞腫の腫瘍発生要因は,依然としてほとんど不明です.

研究の目的:

グループ3およびグループ4の髄芽細胞瘤における腫瘍原発的要因を特定する.
これらの小児脳腫瘍における腫瘍遺伝子の活性化のメカニズムを解明する.

主な方法:

髄芽細胞腫のサンプルにおけるゲノム構造変異の分析.
遺伝子融合とエンハンサー・プロモーターの相互作用の識別.
マウスモデルによる検証.

主要な成果:

グループ3と4の髄芽細胞腫に特異的なゲノム構造変異の有病率が発見されました.
これらの変異は,GFI1とGFI1Bの原発がん遺伝子の活性化につながります.
このメカニズムは,GFI1/GFI1Bのコーディングシーケンスとアクティブエンハンサーを並べ,これを"エンハンサーハイジャック"と呼びます.

結論:

GFI1とGFI1Bは,髄芽細胞腫における重要な腫瘍遺伝子として特定されています.
"エンハンサーハイジャック"は,小児がんにおける腫瘍遺伝子の活性化を促す重要なメカニズムである.
この発見は,髄膜芽細胞腫の新たな治療目標の可能性を提示しています.

さらに関連する動画

10:58

Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma

Published on: February 22, 2015

12.6K

06:32

Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells

Published on: September 1, 2010

16.0K

関連する概念動画

01:33

Cancer-Critical Genes I: Proto-oncogenes

8.9K

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...

8.9K

01:33

Cancer-Critical Genes I: Proto-oncogenes

5.8K

01:06

Induced Pluripotent Stem Cells

4.8K

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...

4.8K

02:38

The Ras Gene

5.7K

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...

5.7K

02:38

Mitogens and the Cell Cycle

6.3K

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...

6.3K

02:33

Hedgehog Signaling Pathway

7.1K

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...