title: Aberrant methylation as a main mechanism of TSGs silencing in PTC.
abstract: 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.
authors.affiliation: Department of Molecular Bases of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Czarnecka
authors.forename: Dorota
authors.initials: D
authors.lastname: Pastuszak-Lewandoska
authors.forename: Monika
authors.initials: M
authors.lastname: Migdalska-Sek
authors.forename: Ewa
authors.initials: E
authors.lastname: Nawrot
authors.forename: Jan
authors.initials: J
authors.lastname: Brzezinski
authors.forename: Marek
authors.initials: M
authors.lastname: Dedecjus
authors.forename: Lech
authors.initials: L
authors.lastname: Pomorski
authors.forename: Ewa
authors.initials: E
authors.lastname: Brzezianska
mesh_terms: D000328:Adult; D001483:Base Sequence; D002277:Carcinoma; D002291:Carcinoma, Papillary; D019175:DNA Methylation / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D020868:Gene Silencing / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D011044:Poland; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013053:Spectrophotometry; D018709:Statistics, Nonparametric; D013447:Sulfites; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000503:physiopathology
chemical_list: D017931:DNA Primers; D013447:Sulfites; C009279:sodium bisulfite