Related Experiment Video
Updated: Jul 15, 2026
11:15
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
A mononucleotide markers panel to identify hMLH1/hMSH2 germline mutations
M Pedroni1, B Roncari, S Maffei
1Department of Medicine and Medical Specialities, University of Modena and Reggio Emilia, Modena, Italy.
Disease Markers
|May 3, 2007
Summary
Testing with two mononucleotide markers (BAT25 and BAT26) is more effective for identifying Lynch syndrome patients with hMLH1/hMSH2 mutations than the Bethesda panel, improving diagnostic specificity and cost-effectiveness.
Area of Science:
- Genetics
- Oncology
- Molecular Diagnostics
Background:
- Hereditary NonPolyposis Colorectal Cancer, also known as Lynch syndrome, is an autosomal dominant condition.
- Germline mutations in DNA repair genes lead to genomic instability, particularly microsatellite instability (MSI), which is found in 85-90% of Lynch syndrome colorectal cancers.
- The Bethesda panel was established to standardize MSI molecular diagnosis.
Purpose of the Study:
- To evaluate the efficacy of using two mononucleotide markers (BAT25 and BAT26) for MSI testing in identifying patients with hMLH1/hMSH2 germline mutations.
- To compare the diagnostic performance of the mononucleotide marker panel against the Bethesda panel for Lynch syndrome diagnosis.
Main Methods:
- Tested 105 tumors for MSI using both the Bethesda panel and the BAT25/BAT26 mononucleotide marker panel.
- Performed immunohistochemical evaluation of MLH1 and MSH2 proteins on tumors with at least one unstable microsatellite.
- Screened for germline hMLH1/hMSH2 mutations in cases with two or more unstable microsatellites.
Main Results:
- The Bethesda panel identified more MSI-positive tumors (49.5%) compared to the mononucleotide panel (28.6%).
- The mononucleotide panel was more efficient in detecting MSI-positive tumors with a lack of MLH1/MSH2 protein expression (93% vs. 54%).
- Germline mutations were found in nearly all patients with MSI-positive tumors and absent MLH1/MSH2 protein expression; no mutations were found in tumors identified solely by dinucleotide markers.
Conclusions:
- The BAT25/BAT26 mononucleotide marker panel demonstrates higher predictive value for identifying hMLH1/hMSH2 mutation-positive Lynch syndrome patients.
- This panel offers increased specificity, enhancing the cost-effectiveness of biomolecular analyses for Lynch syndrome.
- The findings suggest a more efficient diagnostic approach for Lynch syndrome using a targeted mononucleotide marker panel.
