[Frontiers in Bioscience E3, 137-157, January 1, 2011]
Aberrant methylation as a main mechanism of TSGs silencing in PTC
Karolina Czarnecka1, Dorota Pastuszak-Lewandoska1, Monika Migdalska-Sek1, Ewa Nawrot1, Jan Brzezinski2, Marek Dedecjus2, Lech Pomorski3, Ewa Brzezianska1
1Department of Molecular Bases of Medicine, Medical University of Lodz, Pomorska St. 251, 92-213 Lodz, Poland, 2Department of General, Oncological and Endocrine Surgery, Medical University of Lodz, Polish Mother's Memorial Hospital - Research Institute, Rzgowska St. 281/289, 93-338 Lodz, Poland, 3Department of General and Oncological Surgery, Medical University of Lodz, Parzeczewska St. 35, 95-100 Zgierz, Poland
TABLE OF CONTENTS
In the present study the role of tumour suppressor genes (TSGs) hypermethylation and genetic instability of LOH/MSI type in thyroid tumorigenesis was assessed. Expression, methylation status and presence of LOH/MSI were analyzed for 8 TSGs selected from imprinted (IR) and non-imprinted (NIR) chromosomal regions in papillary thyroid carcinomas (PTCs) and nodular goitres (NGs). The results show that methylation-induced gene silencing occurs at an early step of thyroid carcinogenesis and involves multiple genes. Genetic changes of LOH/MSI type are less frequent. In PTC samples, the lack of significant differences in the frequency of LOH in IR and NIR suggests that it is not a key mechanism changing the pattern of gene expression. Co-methylation observed both in NG and PTC raises a possibility that, in thyroid tissue, methylation-induced silencing may occur not only in malignant transformation but also in functional context. We did not recognize any of the studied TSGs - in regard to aberrant methylation status or LOH/MSI frequency - as a selective molecular marker in thyroid tumorigenesis.