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Updated: Dec 19, 2025
Author Spotlight: FISH as a Tool for Precise Gene Amplification Assessment in Cancer Specimens
Published on: July 12, 2024
Semi-comprehensive analysis of gene amplification in thymic malignant tumors using multiplex ligation-dependent probe
Seiichi Kakegawa1, Isao Matsumoto1, Masaya Tamura1
1Department of Thoracic, Cardiovascular and General Surgery, Graduate School of Medical Science, Kanazawa University Ishikawa, Japan.
Abstract:
Research on the amplification of oncogenes in thymic malignant tumor is limited. In this study, we aimed to determine the gene amplification status of receptor tyrosine kinases and other cell regulator genes in thymic malignant tumors, with a view toward the future introduction of molecular targeted therapy. In addition, we examined the usefulness of multiplex, ligation-dependent probe amplification (MLPA) in the semi-comprehensive detection of these gene amplifications. The participants of this study were nine patients with thymic carcinoma and one patient with atypical carcinoid who underwent resection at our department from 1999 to 2016. Twenty-four oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, BRAF, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR) were analyzed for amplification by MLPA. In cases where amplification by MLPA was suspected, confirmation was performed by fluorescence in situ hybridization (FISH). Immunostaining for detected oncoproteins and p53 were performed in cases with confirmed oncogene amplification. MYC (2/10, 20%) and MDM2 (1/10, 10%) amplifications were detected using MLPA and FISH. Immunostaining in both cases was positive. The MDM2-amplified tumor relapsed and spread rapidly after operation despite the use of post-operative chemo-radiotherapy. MYC amplification may be involved in the carcinogenesis of thymic malignant tumors. In addition, MDM2 amplification may be a concern in the increased malignancy.
Insights
Gene amplification of MYC and MDM2 was found in thymic malignant tumors. MDM2 amplification correlated with rapid tumor relapse, suggesting its role in increased malignancy and potential for targeted therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Research on oncogene amplification in thymic malignancies is scarce.
- Understanding gene amplification is crucial for developing targeted therapies.
Purpose of the Study:
- To determine gene amplification status of receptor tyrosine kinases and cell regulators in thymic tumors.
- To evaluate multiplex, ligation-dependent probe amplification (MLPA) for detecting gene amplifications.
- To explore the potential for molecular targeted therapy in thymic malignancies.
Main Methods:
- Analyzed 24 oncogenes for amplification in 10 thymic tumor samples using MLPA.
- Confirmed MLPA findings with fluorescence in situ hybridization (FISH).
- Performed immunostaining for oncoproteins and p53 in confirmed amplification cases.
Main Results:
- Detected MYC amplification in 20% (2/10) and MDM2 amplification in 10% (1/10) of tumors.
- Immunostaining was positive for both detected amplifications.
- The patient with MDM2-amplified tumor experienced rapid relapse despite adjuvant therapy.
Conclusions:
- MYC amplification may contribute to thymic malignant tumor carcinogenesis.
- MDM2 amplification is associated with increased tumor malignancy and rapid progression.
- These findings support further investigation into targeted therapies for thymic malignancies based on gene amplification status.
