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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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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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What is Natural Selection?01:32

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Natural selection is an evolutionary process in which individuals with survival-promoting traits reproduce at higher rates. These favorable traits become more common within a population or species. Naturally selected traits initially arise via random genetic mutations. In order for selection to occur, there must be variation within a population, the trait controlling the variation must be heritable, and there must be an evolutionary advantage for variation in the trait.
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The Evidence for Evolution02:55

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Genetic variations accumulating within populations over generations give rise to biological evolution. Evolutionary changes can result in the formation of novel varieties and entire new species. These changes are responsible for the diverse forms of life inhabiting the planet. The evidence for evolution suggests that all living organisms descended from common ancestors.
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Convergent Evolution01:54

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Evolution shapes the features of organisms over time, ensuring that they are suited for the environments in which they live. Sometimes, selection pressure leads to the rise of similar but unrelated adaptations in organisms with no recent common ancestors, a process known as convergent evolution.
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Characterizing Mutational Load and Clonal Composition of Human Blood
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Cancer evolution, mutations, and clonal selection in relapse neuroblastoma.

Marc Schulte1, Johannes Köster2, Sven Rahmann2,3

  • 1Molecular Oncology, Internal Medicine/Cancer Research Unit, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany. marc.schulte@uk-essen.de.

Cell and Tissue Research
|February 26, 2018
PubMed
Summary

Cancer evolves like a complex system, with childhood neuroblastoma showing more genetic changes upon relapse. Understanding tumor evolution is key for developing targeted treatments.

Keywords:
Clonal selectionIntratumoral heterogeneityNeuroblastomaPediatricRelapse

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Area of Science:

  • Oncology
  • Evolutionary Biology
  • Genetics

Background:

  • Cancer progression is viewed as an evolutionary process driven by genetic alterations and cellular plasticity.
  • Cancer cells develop resistance to treatments, immune attacks, and evade normal growth constraints.
  • Metastasis, organ homing, and anoikis resistance mechanisms are poorly understood aspects of cancer evolution.

Purpose of the Study:

  • To review findings on genetic events in relapsing neuroblastoma, a childhood cancer.
  • To explore the evolutionary dynamics of neuroblastoma under treatment pressure.
  • To provide an outlook on managing intratumoral heterogeneity for future neuroblastoma therapies.

Main Methods:

  • Analysis of genetic events in primary versus relapsing neuroblastoma.
  • Assessment of single nucleotide variants (SNVs) and allelic frequency shifts.
  • Review of previously reported data on tumor evolution.

Main Results:

  • Relapsing neuroblastoma tumors exhibit significantly higher single nucleotide variants compared to primary tumors.
  • Evidence suggests branched tumor evolution and clonal selection under treatment.
  • Shifts in allelic frequencies indicate dynamic changes between primary and relapsed stages.

Conclusions:

  • Neuroblastoma exhibits complex evolutionary patterns, including branched evolution and clonal selection.
  • Intratumoral heterogeneity and sub-clonal diversity are critical challenges in neuroblastoma treatment.
  • Future therapeutic strategies must address these evolutionary dynamics for effective targeted treatments.