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Microsatellite instability in sporadic endometrial carcinoma
B D Duggan1, J C Felix, L I Muderspach
1Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles.
Journal of the National Cancer Institute
|August 17, 1994
Summary
The replication error (RER) positive phenotype, indicating microsatellite instability, is common in sporadic endometrial cancer. This genomic instability appears early in tumor development, contributing to cancer progression.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Somatic microsatellite mutations are observed in various cancers, including endometrial carcinoma.
- The replication error (RER) or mutator phenotype is a key characteristic of these mutations.
Purpose of the Study:
- To determine the frequency and nature of the RER phenotype in sporadic endometrial cancer.
- To investigate the timing of RER acquisition relative to tumor clonal expansion.
Main Methods:
- Screening of 45 sporadic endometrial cancer tissues for RER phenotype at three microsatellite loci.
- Analysis of microsatellite sizes using selective UV radiation fractionation to assess timing of alterations.
- PCR amplification and analysis of microsatellite and c-K-ras gene loci.
Main Results:
- The RER positive (RER+) phenotype was found in 20% of sporadic endometrial carcinomas.
- RER+ was present in primary tumors and metastases but absent in adjacent normal/hyperplastic endometrium.
- Mutant c-K-ras alleles were more frequent in RER+ tumors, suggesting acquisition after RER+ phenotype.
Conclusions:
- The RER+ phenotype is frequent in sporadic endometrial cancer and precedes or occurs during clonal expansion.
- The diverse RER+ phenotypes suggest heterogeneous underlying mutator mutations.
- Genomic instability, indicated by RER+, likely contributes to endometrial cancer transformation.