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World Congress on Thyroid Cancer 4.0
July 29 – August 1, 2021
Genomic Instability, MLH1 and MGMT Expression in Thyroid Carcinoma
- Presentation Speakers / Moderators
Microsatellite instability (MSI), caused by defects in the mismatch repair pathway, is a phenotype frequently associated with various human malignancies. Interestingly, promoter hypermethylation of the mismatch repair genes Human Mut-L Homologue 1 (MLH1) and O6-methylguanine DNA methyltransferase (MGMT) has been documented in several types of human cancers. Loss of MGMT expression may be the underlying mechanism associated with presence of BRAF V600E, RAS, IDH1, PIK3CA mutations and/or other genetic alterations found in thyroid tumours.
The aim of the present work was to investigate the methylation status and expression levels of MLH1, MGMT genes and microsatellite instability (MSI) in a series of benign and malignant thyroid lesions.
The study was conducted on 30 thyroid tissue samples obtained from patients who underwent thyroid surgery for thyroid cancer. Malignant and normal tissue samples were obtained from each patient.
Detection of MLH1 and MGMT methylation status in thyroid carcinoma and normal tissue samples was carried out by MS-PCR after bisulphite treatment. MSI assessment was done on QIAxcel advanced system capillary electrophoresis after paired PCR reactions containing patient-matched normal and tumor DNA.
Malignant thyroid tissues showed significant hypermethylation of both MLH1 and MGMT genes compared to the benign thyroid samples (p<0.001, p=0.02 respectively). The relative expression patterns of MLH1 and MGMT were significantly downregulated in the malignant thyroid tissue samples.
DISCUSSION AND CONCLUSION
The results revealed that MSI and hypermethylation of MMR system genes may play an important role in the pathogenesis and outcome of thyroid carcinoma.
Two Approaches to Level 5 Neck Dissection
- Jeff Blumberg