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Updated: Feb 4, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Detection of MAPK/ERK pathway proteins and KRAS mutations in adenomatoid odontogenic tumors
Ronell Bologna-Molina1, Ikuko Ogawa2, Adalberto Mosqueda-Taylor3
1Molecular Pathology Area, Faculty of Dentistry, Universidad de la República, Montevideo, Uruguay.
Objective:
This study aimed to assess the frequency of KRAS mutation and its association with the presence of the MAPK/ERK signaling pathway proteins in adenomatoid odontogenic tumors.
Study Design:
Paraffin-embedded tissue samples from nine cases of adenomatoid odontogenic tumor were used. Genomic DNA was extracted from each sample; in one case, genetic mutations in 50 cancer-associated genes were examined by next-generation sequencing. Hotspot mutations in the RAS family were analyzed by Luminex assay using the remaining eight cases. Subsequently, immunohistochemistry for KRAS, CRAF, BRAF, EGFR, ERK, MEK, and BRAFV600E was performed.
Results:
A KRAS G12D missense mutation was detected in the DNA sequence of the tumor cells, but it was not detected in the stromal tissue. KRAS G12V and KRAS G12R mutations were detected in two and four cases, respectively. For immunohistochemistry, all the cases were EGFR, KRAS, BRAF, CRAF positive, one case was ERK negative,and one case was MEK and ERK negative, all the other remaining cases were MEK and ERK positive.
Conclusion:
KRAS mutation at codon 12 and the presence of MAPK/ERK pathway proteins were detected suggesting their association with tumorigenesis of adenomatoid odontogenic tumors.
Insights
KRAS mutations were found in adenomatoid odontogenic tumors, alongside MAPK/ERK pathway proteins, suggesting a role in tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Adenomatoid odontogenic tumors (AOTs) are rare benign neoplasms.
- The molecular mechanisms underlying AOT development are not fully understood.
- Investigating genetic mutations and signaling pathways can elucidate AOT pathogenesis.
Purpose of the Study:
- To determine the frequency of KRAS mutations in AOTs.
- To assess the presence of MAPK/ERK signaling pathway proteins in AOTs.
- To explore the association between KRAS mutations and MAPK/ERK pathway proteins in AOTs.
Main Methods:
- Analysis of paraffin-embedded AOT tissue samples (n=9).
- Genomic DNA extraction and next-generation sequencing for mutation analysis.
- Luminex assay for RAS family mutations and immunohistochemistry for pathway proteins (KRAS, CRAF, BRAF, EGFR, ERK, MEK, BRAFV600E).
Main Results:
- KRAS mutations (G12D, G12V, G12R) were detected in tumor cells.
- All cases showed positive expression for EGFR, KRAS, BRAF, and CRAF.
- Most cases exhibited positive expression for MEK and ERK, with some exceptions.
Conclusions:
- KRAS mutations at codon 12 are present in AOTs.
- MAPK/ERK pathway proteins are present in AOTs.
- These findings suggest a potential association between KRAS mutations, MAPK/ERK pathway activation, and AOT tumorigenesis.
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