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CancerQuest > Introduction to Cancer Biology > Introduction to Mutation > Section Summary: Genetic Change

Section Summary: Genetic Change

Genetic Change (Mutation) Introduction

• The abnormal behaviors demonstrated by cancer cells are the result of a series of mutations in key regulatory genes (i.e. DNA repair genes).
• Most cancers are thought to arise from a single precursor cell that acquires sufficient mutations to become a cancerous cell.

 

DNA Mutations

• Genetic changes can be small, affecting only one or a few nucleotides (point mutations) or they may be quite large, alter the structure of a chromosome or chromosomes.
• Point Mutations
  • Translation is the production of a protein by enzymes that 'read' three nucleotide 'words' (codons) along a messenger RNA (mRNA).
  • Even changing a single nucleotide along the DNA of a gene may lead to a completely non-functional protein. The mutations are grouped according to the changes they create in the resulting protein product of the affected gene.
    • Nonsense mutations - The new (mutant) codon causes protein synthesis to stop prematurely.
    • Missense mutations - The altered codon results in the insertion of an incorrect amino acid into the protein.
    • Frameshift mutations - The loss or gain of 1 or 2 nucleotides in an mRNA causes codons to be misread. Frequently results in shortened and non-functional proteins.
• Chromosome Level Changes
  • Translocations - Breakage and (sometimes) exchange of chromosome fragments.
  • Gene amplification - Abnormal replication creates multiple copies of a region of a chromosome. Ultimately this leads to overproduction of the corresponding proteins.
  • Inversions - Segments of DNA are released from a chromosome and then re-inserted in the opposite orientation.
  • Duplications/Deletions - A gene or group of genes may be lost altogether or copied more than one time within a chromosome.
  • Aneuploidy - A genetic change that involves the loss or gain of entire chromosomes.
• Spontaneous mutations can occur due to unrepaired DNA or random molecular events.
• Aneuploidy is very common in cancer cells.

 

Epigenetic Changes

• Gene expression can be altered by changes to the DNA and chromatin that do not change the genetic sequence. Examples include DNA methylation and acetylation of histones.
• Methylation - Some nucleotides in the DNA are modified by the addition of a methyl group which is associated with the inactivation of that region of DNA
• Acetylation - Addition of acetyl groups loosens the DNA and increases gene expression.

 

Induced Mutations

• Mutations can be induced by exposing organisms (or cells) to a variety of treatments:
  • Radiation - UV rays cause point mutations and X-rays cause multiple forms of damage.
  • Chemical mutagens - Can bind to DNA or the building blocks of DNA and interfere with the replication or transcription processes.
  • Chronic inflammation - DNA damage due to the production of mutagenic chemicals by the cells of the immune system
  • Oxygen radicals - Results from a cell's energy production and can damage DNA.

 

Other Genetic Changes

• Aberrant cell division resulting in incorrect division of the chromosomes can lead to aneuploidy.
• Viruses can cause genetic damage in several different ways and are associated with a wide range of cancers.

 

Mutation and Cancer

• It seems the transition from a normal, healthy cell to a cancer cell is a stepwise progression.
• Cancer development requires genetic changes in several different oncogenes and tumor suppressors.
• All cancers have to overcome the same spectrum of regulatory functions in order to grow and progress, but the genes involved may differ.
• The heterogeneity of cancer complicates diagnosis and treatment.
• It is possible to inherit dysfunctional genes leading to the development of a familial form of a particular cancer type.