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Following the Dynamics of Structural Variants in Experimentally Evolved Populations
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Microsatellite instability: an update.

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Microsatellite instability (MSI) arises from deficient DNA mismatch repair (MMR) and is key in Lynch syndrome cancers. MSI analysis aids in identifying Lynch syndrome and predicting chemotherapy response.

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Area of Science:

  • Oncology
  • Genetics
  • Epigenetics

Background:

  • Deficient DNA mismatch repair (MMR) leads to microsatellite instability (MSI), a hallmark of Lynch syndrome-associated cancers.
  • MSI involves length alterations in microsatellites and is caused by mutations or epimutations in MMR genes (MLH1, MSH2, MSH6, PMS2).
  • MSI is also found in sporadic colorectal, gastric, and endometrial cancers, often linked to MLH1 hypermethylation.

Purpose of the Study:

  • To review recent advances in the pathogenesis of MSI.
  • To highlight genome-wide analyses identifying MSI and related alterations as potential biomarkers and therapeutic targets.
  • To summarize the role of MSI in cancer development and clinical applications.

Main Methods:

  • Review of existing literature on MSI pathogenesis and molecular characterizations.
  • Analysis of data from The Cancer Genome Atlas for colorectal, endometrial, and gastric cancers.
  • Examination of genetic, epigenetic, and transcriptomic differences in MSI+ cancers.

Main Results:

  • MSI+ cancers are distinct biological entities with unique molecular profiles.
  • BRAF V600E mutation is associated with sporadic MSI+ CRCs but not Lynch syndrome-related CRCs.
  • Interactions between MSI and microRNA (miRNA) are implicated in MSI+ cancer pathogenesis, with altered miRNA expression affecting MMR genes.

Conclusions:

  • MSI analysis is crucial for identifying Lynch syndrome and serves as a prognostic factor for chemotherapy.
  • MSI and its related molecular alterations represent promising biomarkers and therapeutic targets.
  • Understanding MSI pathogenesis provides insights into cancer development and personalized treatment strategies.