title: Amplification of thymosin beta 10 and AKAP13 genes in metastatic and aggressive papillary thyroid carcinomas.
abstract: Papillary thyroid carcinoma (PTC) is the most common well-differentiated thyroid cancer. Although the great majority of the cases exhibit an indolent clinical course, some of them develop local invasion with distant metastasis, and a few cases transform into undifferentiated/anaplastic thyroid carcinoma with a rapidly lethal course. To identify gene copy number alterations predictive of metastatic potential or aggressive transformation, array-based comparative genomic hybridization (CGH-array) was performed in 43 PTC cases. Formalin-fixed and paraffin-embedded samples from primary tumours of 16 cases without metastasis, 14 cases with only regional lymph node metastasis, and 13 cases with distant metastasis, recurrence or extrathyroid extension were analysed. The CGH-array and confirmatory quantitative real-time PCR results identified the deletion of the EIF4EBP3 and TRAK2 gene loci, while amplification of thymosin beta 10 (TB10) and Tre-2 oncogene regions were observed as general markers for PTC. Although there have been several studies implicating TB10 as a specific marker based on gene expression data, our study is the first to report on genomic amplification. Although no significant difference could be detected between the good and bad prognosis cases in the A-kinase anchor protein 13 (AKAP13) gene region, it was discriminative markers for metastasis. Amplification in the AKAP13 region was demonstrated in 42.9% and 15.4% of the cases with local or with distant metastasis, respectively, while no amplification was detected in non-metastatic cases. AKAP13 and TB10 regions may represent potential new genomic markers for PTC and cancer progression.
authors.affiliation: Laboratory of Functional Genomics, Biological Research Centre, Hungarian Academy of Sciences, P.O. Box 521, Szeged, 6701, Hungary.
authors.forename: Liliána Z
authors.initials: LZ
authors.lastname: Fehér
authors.forename: Gábor
authors.initials: G
authors.lastname: Pocsay
authors.forename: László
authors.initials: L
authors.lastname: Krenács
authors.forename: Agnes
authors.initials: A
authors.lastname: Zvara
authors.forename: Enikő
authors.initials: E
authors.lastname: Bagdi
authors.forename: Réka
authors.initials: R
authors.lastname: Pocsay
authors.forename: Géza
authors.initials: G
authors.lastname: Lukács
authors.forename: Ferenc
authors.initials: F
authors.lastname: Győry
authors.forename: Andrea
authors.initials: A
authors.lastname: Gazdag
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Tarkó
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D013947:Thymosin / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D015778:Minor Histocompatibility Antigens; D011518:Proto-Oncogene Proteins; D013947:Thymosin; C039302:thymosin beta(10)