人間の癌ゲノムにおける体的変異のパターン
Christopher Greenman1, Philip Stephens, Raffaella Smith
1Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Nature
|March 9, 2007
まとめ
研究者はがんゲノムを配列化し,タンパク質キナーゼ遺伝子の1000以上の変異を特定しました. この研究は,約120のドライバー遺伝子を含み,既知の癌遺伝子のレパートリーを拡大しています.
科学分野:
- ゲノミクスゲノミクスとは
- がん生物学 がん生物学
- 分子腫瘍学 分子腫瘍学
背景:
- 癌の発症は,細胞成長の利点を授与する遺伝子変異によって引き起こされる.
- ヒトゲノムシーケンシングの出現は,系統的な変異分析を通じて,新しいがん遺伝子の識別を容易にする.
研究 の 目的:
- 癌ゲノムを体系的に再配列化して,がんに関連した遺伝子をさらに発見する.
- ヒトの様々ながんにおけるタンパク質キナーゼ遺伝子の体内変異を分析する.
主な方法:
- 518のタンパク質キナーゼ遺伝子からのコードエグソンの全エクソーム配列化.
- 210の多様なヒトがんサンプルから274メガベース (Mb) のDNAを分析した.
- 1,000以上の体変異の識別と特徴付け.
主要な成果:
- ヒトの210種類の癌のタンパク質キナーゼ遺伝子で1,000以上の体内変異が特定されました.
- 暴露,DNA修復,および細胞起源に関連した,観察された突然変異パターンの有意な変動.
- 証拠によると,約120の遺伝子が,腫瘍発生に寄与する原動力変異を宿していることが示唆されています.
結論:
- 癌の系統的なゲノム配列解析は,がんにおける広範な進化的多様性を明らかにしています.
- がん遺伝子のレパートリーは,これまで考えられていたよりも多く,がんの発症に関与している.
- ドライバー変異の識別は,がんのメカニズムと潜在的な治療目標の洞察を提供します.
関連する概念動画
02:18Cancer
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
01:12Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
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...
02:21Cancers Originate from Somatic Mutations in a Single Cell
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
01:12Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...