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Amplification of Thymosin Beta 10 and AKAP13 Genes in Metastatic and Aggressive Papillary Thyroid Carcinomas

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Pathology & Oncology Research

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.

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Abbreviations

AKAP13:

A-kinase anchor protein 13

BPTC:

Papillary thyroid carcinoma with a bad disease outcome

CGH-array:

Array-based comparative genomic hybridization

DOP-PCR:

Degenerate oligonucleotide-primed PCR

EIF4EBP3:

Eukaryotic initiation factor 4E-binding protein 3

FGF7:

Fibroblast growth factor 7

GPTC:

Papillary thyroid carcinoma with a good disease outcome

GPTC1:

Papillary thyroid carcinoma with a good disease outcome without metastasis

GPTC2:

Papillary thyroid carcinoma with a good disease outcome with regional lymph node metastasis

LOH:

Loss of heterozygosity

PTC:

Papillary thyroid carcinoma

QRT-PCR:

Quantitative real-time polymerase chain reaction

TB10:

Thymosin beta 10

TRAK2:

Trafficking protein, kinesin binding 2

UTC:

Undifferentiated thyroid carcinoma

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Acknowledgements

This work was supported by grants from the Hungarian Ministry of Health (ETT 400/2003) and a bilateral grant between the Hungarian Prime Minister’s Office and the Hungarian Academy of Sciences (40.232/1/2005), the Economic Development Oriented Project of the Békés County Self-Government and the Berkes Foundation of the Pándy Kálmán County Hospital, Gyula. We would also like to thank the Jósa András County Hospital in Nyíregyháza, the Erzsébet Hospital in Hódmezővásárhely, the County Hospital in Kecskemét, the Pándy Kálmán County Hospital in Gyula, and especially Z. Nemes, Department of Pathology, Medical and Health Science Center, University of Debrecen, Hungary, for providing the thyroid carcinoma samples.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Functional Genomics, Biological Research Centre, Hungarian Academy of Sciences, P.O. Box 521, Szeged, 6701, Hungary

    Liliána Z. Fehér, Ágnes Zvara & László G. Puskás

  2. 1st Department of Internal Medicine, Pándy Kálmán County Hospital, Gyula, Hungary

    Gábor Pocsay, Réka Pocsay & Andrea Gazdag

  3. Laboratory of Tumour Pathology and Molecular Diagnostics, Szeged, Hungary

    László Krenács & Enikő Bagdi

  4. 1st Department of Surgery, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary

    Géza Lukács & Ferenc Győry

  5. 2nd Department of Internal Medicine, Borsod-Abaúj-Zemplén County Hospital, Miskolc, Hungary

    Erzsébet Tarkó

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  1. Liliána Z. Fehér
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  2. Gábor Pocsay
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  10. Erzsébet Tarkó
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Correspondence to László G. Puskás.

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Fehér, L.Z., Pocsay, G., Krenács, L. et al. Amplification of Thymosin Beta 10 and AKAP13 Genes in Metastatic and Aggressive Papillary Thyroid Carcinomas. Pathol. Oncol. Res. 18, 449–458 (2012). https://doi.org/10.1007/s12253-011-9467-7

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