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Mutations in Mismatch Repair Genes and Microsatellite Instability Status in Pancreatic Cancer
Marina Emelyanova1, Anna Ikonnikova1, Alexander Pushkov2
1Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
Cancers
|June 19, 2024
Summary
Microsatellite instability (MSI) is rare in pancreatic cancer (PC), even with mismatch repair (MMR) gene mutations. This study found no MSI-high tumors, highlighting the need to assess MMR deficiency in PC patients with Lynch syndrome before immunotherapy.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Pancreatic cancer (PC) patients with mismatch repair (MMR) deficiency may respond to immunotherapy.
- Microsatellite instability (MSI) is a key indicator of MMR deficiency (MMR-D).
Purpose of the Study:
- To determine the prevalence of MSI in PC.
- To investigate germline and somatic mutations in MMR genes (MLH1, MSH2, MSH6).
- To assess the link between MMR gene mutations and MSI status in PC.
Main Methods:
- Targeted next-generation sequencing of clinical specimens from PC patients (paired normal/tumor, tumor-only, normal-only).
- MSI status assessment using PCR in 235 PC cases.
- Identification and analysis of germline and somatic variants in MMR genes.
Main Results:
- Pathogenic/likely pathogenic germline variants in MMR genes found in 1.1% of patients; somatic variants in 2.6%.
- No microsatellite instability-high (MSI-H) tumors were detected in the study cohort.
- MSI is infrequent in PC, even in tumors harboring MMR gene mutations.
Conclusions:
- MSI is rare in pancreatic cancer.
- Assessing tumor MMR-D status is crucial for PC patients with Lynch syndrome considering immunotherapy.
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