microsatellite instability

Introduction

Instability in VNTR? Originally studied to identify loss of heterozygosity.

Epidemiology

• 3% of colorectal cancer & endometrial cancers are associated with Lynch syndrome.

Pathology

• microsatellite instability may occur as a result of dysfunction of DNA mismatch repair
• microsatellite instability occurs in the germline of patients with hereditary nonpolyposis colorectal cancer (Lynch syndrome) & in 15% of sporadic colorectal cancers
  • mismatch repair deficiency involving BAT25, BAT26
  • microsatellite instability increases odds of Lynch syndrome
• only 1/2 of cancers with Lynch syndrome abnormalities are colorectal cancer or endometrial cancer
  • other tumors associated with Lynch syndrome
    • prostate cancer, sarcomas, mesothelioma, adrenocortical carcinoma, ovarian germ-cell tumor small intestinal cancer, gastric cancer

Genetics

• repetitive sequences of DNA
• relatively high rates of mutation
• may contribute to the rapid evolution of species-typical traits
• alleles of repetitive polymorphic microsatellites in the 5' region of a gene may serve regulatory functions & confer individual differences in gene expression & may contribute to normal variation in behavioral traits

Management

• for patients with colorectal cancer, microsatellite instability correlates with longer recurrence-free survival after surgical resection with or without adjuvant chemotherapy
• pembrolizumab (Keytruda) FDA-approved for treatment of any unresectable or metastatic tumor with microsatellite instability

More general terms

• chromosomal instability
• molecular diagnostic test

Additional terms

• DNA mismatch repair; post-replication repair; DNA loop repair
• microsatellite or variable number of tandem repeat (VNTR)