Not the same thing: metastatic PTCs have a different background than ATCs
Anaplastic thyroid cancer (ATC) is a rare but highly aggressive form of thyroid cancer. By contrast, differentiated papillary thyroid cancer (PTC) only rarely behave aggressively and develop distant metastasis. Whether distantly metastatic PTC (DM-PTC) and ATC share a common genetic background is st...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Bioscientifica
2018-11-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/7/12/EC-18-0386.xml |
| _version_ | 1828403458375417856 |
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| author | Dario de Biase Federica Torricelli Moira Ragazzi Benedetta Donati Elisabetta Kuhn Michela Visani Giorgia Acquaviva Annalisa Pession Giovanni Tallini Simonetta Piana Alessia Ciarrocchi |
| author_facet | Dario de Biase Federica Torricelli Moira Ragazzi Benedetta Donati Elisabetta Kuhn Michela Visani Giorgia Acquaviva Annalisa Pession Giovanni Tallini Simonetta Piana Alessia Ciarrocchi |
| author_sort | Dario de Biase |
| collection | DOAJ |
| description | Anaplastic thyroid cancer (ATC) is a rare but highly aggressive form of thyroid cancer. By contrast, differentiated papillary thyroid cancer (PTC) only rarely behave aggressively and develop distant metastasis. Whether distantly metastatic PTC (DM-PTC) and ATC share a common genetic background is still to be defined. We used next-generation sequencing (NGS) to explore the genetic background of a cohort of ATC and DM-PTC and a group of well-differentiated PTCs that did not developed distant metastasis as control (ctrl-PTC). A panel of 128 amplicons within 21 thyroid cancer-related genes
was analyzed in a set of 151 thyroid cancer samples including 66 ATCs and DM-PTCs.
We showed that the ATC/DM-PTC group had an overall mutational load higher than
ctrl-PTCs and that ATCs and DM-PTCs are characterized by a different genetic background, with the exception of mutations in the TERT promoter that were overrepresented in both ATCs (61.1%) and DM-PTCs (48.2%) vs non-aggressive ctrl-PTCs (7.6%). In ATCs, TERT promoter mutations were frequently associated with TP53 mutations, while in the DM-PTCs no significant co-occurrence was observed. No significant association of MED12 mutations with aggressiveness of thyroid cancer was observed in our analysis. Finally, correlation analysis showed that increasing number of mutations negatively impact on patient overall survival also within the ATC and DM-PTC group. In conclusions, overall our analysis further highlights the relevance of TERT promoter mutations in driving aggressiveness and provides new pieces of information in the definition of aggressiveness evolution of thyroid cancer lesions. |
| first_indexed | 2024-12-10T10:19:39Z |
| format | Article |
| id | doaj.art-cc1f8a2ad80e46b29a69ef54f13508d5 |
| institution | Directory Open Access Journal |
| issn | 2049-3614 2049-3614 |
| language | English |
| last_indexed | 2024-12-10T10:19:39Z |
| publishDate | 2018-11-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-cc1f8a2ad80e46b29a69ef54f13508d52022-12-22T01:52:55ZengBioscientificaEndocrine Connections2049-36142049-36142018-11-0171213701379https://doi.org/10.1530/EC-18-0386Not the same thing: metastatic PTCs have a different background than ATCsDario de Biase0Federica Torricelli1Moira Ragazzi2Benedetta Donati3Elisabetta Kuhn4Michela Visani5Giorgia Acquaviva6Annalisa Pession7Giovanni Tallini8Simonetta Piana9Alessia Ciarrocchi10Department of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie) – Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, Bologna, ItalyLaboratory of Translational Research, Azienda Unità Sanitaria Locale AUSL-IRCCS, Reggio Emilia, ItalyPathology Unit, Azienda Unità Sanitaria Locale AUSL-IRCCS, Reggio Emilia, ItalyLaboratory of Translational Research, Azienda Unità Sanitaria Locale AUSL-IRCCS, Reggio Emilia, ItalyPathology Unit, Azienda Unità Sanitaria Locale AUSL-IRCCS, Reggio Emilia, ItalyDepartment of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale) – Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna School of Medicine, Bologna, ItalyDepartment of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale) – Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna School of Medicine, Bologna, ItalyDepartment of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie) – Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, Bologna, ItalyDepartment of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale) – Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna School of Medicine, Bologna, ItalyPathology Unit, Azienda Unità Sanitaria Locale AUSL-IRCCS, Reggio Emilia, ItalyLaboratory of Translational Research, Azienda Unità Sanitaria Locale AUSL-IRCCS, Reggio Emilia, ItalyAnaplastic thyroid cancer (ATC) is a rare but highly aggressive form of thyroid cancer. By contrast, differentiated papillary thyroid cancer (PTC) only rarely behave aggressively and develop distant metastasis. Whether distantly metastatic PTC (DM-PTC) and ATC share a common genetic background is still to be defined. We used next-generation sequencing (NGS) to explore the genetic background of a cohort of ATC and DM-PTC and a group of well-differentiated PTCs that did not developed distant metastasis as control (ctrl-PTC). A panel of 128 amplicons within 21 thyroid cancer-related genes was analyzed in a set of 151 thyroid cancer samples including 66 ATCs and DM-PTCs. We showed that the ATC/DM-PTC group had an overall mutational load higher than ctrl-PTCs and that ATCs and DM-PTCs are characterized by a different genetic background, with the exception of mutations in the TERT promoter that were overrepresented in both ATCs (61.1%) and DM-PTCs (48.2%) vs non-aggressive ctrl-PTCs (7.6%). In ATCs, TERT promoter mutations were frequently associated with TP53 mutations, while in the DM-PTCs no significant co-occurrence was observed. No significant association of MED12 mutations with aggressiveness of thyroid cancer was observed in our analysis. Finally, correlation analysis showed that increasing number of mutations negatively impact on patient overall survival also within the ATC and DM-PTC group. In conclusions, overall our analysis further highlights the relevance of TERT promoter mutations in driving aggressiveness and provides new pieces of information in the definition of aggressiveness evolution of thyroid cancer lesions.https://ec.bioscientifica.com/view/journals/ec/7/12/EC-18-0386.xmlhighly aggressive thyroid cancergenetic profileTERT promoter mutationsanaplastic thyroid cancerpapillary thyroid cancerMED12 mutations |
| spellingShingle | Dario de Biase Federica Torricelli Moira Ragazzi Benedetta Donati Elisabetta Kuhn Michela Visani Giorgia Acquaviva Annalisa Pession Giovanni Tallini Simonetta Piana Alessia Ciarrocchi Not the same thing: metastatic PTCs have a different background than ATCs Endocrine Connections highly aggressive thyroid cancer genetic profile TERT promoter mutations anaplastic thyroid cancer papillary thyroid cancer MED12 mutations |
| title | Not the same thing: metastatic PTCs have a different background than ATCs |
| title_full | Not the same thing: metastatic PTCs have a different background than ATCs |
| title_fullStr | Not the same thing: metastatic PTCs have a different background than ATCs |
| title_full_unstemmed | Not the same thing: metastatic PTCs have a different background than ATCs |
| title_short | Not the same thing: metastatic PTCs have a different background than ATCs |
| title_sort | not the same thing metastatic ptcs have a different background than atcs |
| topic | highly aggressive thyroid cancer genetic profile TERT promoter mutations anaplastic thyroid cancer papillary thyroid cancer MED12 mutations |
| url | https://ec.bioscientifica.com/view/journals/ec/7/12/EC-18-0386.xml |
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