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Genomic instability: first step to carcinogenesis.

C Schmutte1, R Fishel

  • 1Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA. cschmutte@hendrix.jci.tju.edu

Anticancer Research
|March 4, 2000
PubMed
Summary
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Genomic instability, driven by genetic and epigenetic changes, may initiate cancer. Understanding these DNA repair and methylation alterations can improve cancer diagnosis and treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Human cancers frequently exhibit multiple genetic alterations.
  • Inactivation of DNA repair pathways can increase mutation rates and chromosomal instability, potentially initiating cancer.
  • Epigenetic changes, such as DNA methylation alterations, are also early events in tumorigenesis.

Purpose of the Study:

  • To explore the role of genomic instability, encompassing both genetic and epigenetic alterations, as a potential initial step in carcinogenesis.
  • To highlight the significance of understanding DNA repair and methylation mechanisms for advancing cancer diagnosis and therapy.

Main Methods:

  • Review of existing literature on genetic alterations in cancer.
  • Examination of evidence linking DNA repair pathway inactivation to cancer development.

Related Experiment Videos

  • Analysis of studies on epigenetic changes, specifically DNA methylation patterns, in early tumorigenesis.

    • Main Results:

    • Inactivation of DNA repair pathways, like mismatch repair (linked to Hereditary Nonpolyposis Colorectal Cancer), is implicated in cancer initiation and progression.
    • Accumulating evidence suggests frequent inactivation of various DNA repair pathways across different cancer types.
    • Both local hypermethylation and genome-wide hypomethylation are common early epigenetic alterations in cancer.

    Conclusions:

    • Genomic instability, resulting from genetic and/or epigenetic alterations, may represent the foundational event in cancer development.
    • Further knowledge of these underlying biochemical mechanisms is crucial for developing more effective cancer diagnostic tools and therapeutic strategies.