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Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

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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...
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Mutations01:39

Mutations

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Overview
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Mutations01:35

Mutations

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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
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Viral Mutations00:36

Viral Mutations

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Cell Lines01:16

Cell Lines

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A cell line is a population of cells grown in vitro that can be subcultured over several generations. Normal cells cease to divide after a certain number of cell divisions, a process known as replicative senescence. This number, called the Hayflick limit, was conceptualized by Leonard Hayflick in 1961 when he observed that fetal cells grown in culture could only divide 40-60 times. This limit is due to the shortening of the telomeres during each round of cell division, preventing cell division...
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In-vitro Mutagenesis01:16

In-vitro Mutagenesis

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To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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  2. ヒトの癌細胞系における突然変異の特徴は,エピソード的apobec変異を明らかにする
  1. ホーム
  2. ヒトの癌細胞系における突然変異の特徴は,エピソード的apobec変異を明らかにする

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Characterizing Mutational Load and Clonal Composition of Human Blood
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Characterizing Mutational Load and Clonal Composition of Human Blood

Published on: July 11, 2019

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ヒトの癌細胞系における突然変異の特徴は,エピソード的APOBEC変異を明らかにする

Mia Petljak1, Ludmil B Alexandrov2, Jonathan S Brammeld1

  • 1Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.

Cell
|March 9, 2019

PubMed で要約を見る

まとめ
この要約は機械生成です。

がん細胞系は 進行中の変異パターンを示しています DNAの修復と複製のシグネチャは安定している一方で APOBECの編集は変動する 爆発的な活動を示し 癌ゲノム進化の洞察を提供します

キーワード:
APOBECデアミナーゼがん細胞系エピソード性突然変異変異シグネチャー異種移植

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Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders
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Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders

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Characterizing Mutational Load and Clonal Composition of Human Blood
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Characterizing Mutational Load and Clonal Composition of Human Blood

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Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
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Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders
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Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders

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科学分野:

  • ゲノミクス
  • 癌 生物学
  • 分子生物学

背景:

  • 癌ゲノムを理解する鍵となるものです 癌ゲノムを理解する鍵となるものです
  • 以前の研究では,がん細胞系と異種移植で共通する突然変異のサインを特定しました.

研究 の 目的:

  • 癌細胞系における突然変異のシグネチャー生成の進行パターンを調査する.
  • 外部変異因子や内生的なプロセスが継続的なシグネチャー形成を誘発するかどうかを判断する.

主な方法:

  • ヒトの癌細胞系を 長期にわたって培養する
  • 変異パターンを分析するために 培養細胞のDNA配列解析
  • in vitroで生成されたシグネチャと,既知の in vivoシグネチャを比較する.

主要な成果:

  • タバコの煙や紫外線などの外部からの曝露によるシグネチャーは in vitro で生成されませんでした.
  • DNAの修復と複製に関連するシグネチャーが一貫して生成されました.
  • APOBECサイチジンデアミナーゼのシグネチャーは,エピソード的な勃発で,大きな時間的な変動を示した.

結論:

  • がん細胞系は進行中の内生的な変異プロセスをモデル化することができます.
  • APOBECの活動は,レトロトランスポゾンを含む可能性のある不明な開始因子による爆発によって特徴付けられています.
  • これらの細胞系はヒトの癌の変異過程を研究するための貴重な実験モデルとして機能します.