Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent <i>AIFM3</i> and <i>DLK1</i> Copy Gain in Medullary Thyroid Carcinoma
Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid C-cells that can occur either in sporadic (70–80%) or hereditary (20–30%) form. In this study we aimed to identify recurrent copy number alterations (CNA) that might be related to the pathogenesis or progression of MTC....
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MDPI AG
2021-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/2/218 |
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| author | Aline Neves Araujo Cléber Pinto Camacho Thais Biude Mendes Susan Chow Lindsey Lais Moraes Marta Miyazawa Rosana Delcelo Renata Pellegrino Diego Robles Mazzotti Rui Monteiro de Barros Maciel Janete Maria Cerutti |
| author_facet | Aline Neves Araujo Cléber Pinto Camacho Thais Biude Mendes Susan Chow Lindsey Lais Moraes Marta Miyazawa Rosana Delcelo Renata Pellegrino Diego Robles Mazzotti Rui Monteiro de Barros Maciel Janete Maria Cerutti |
| author_sort | Aline Neves Araujo |
| collection | DOAJ |
| description | Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid C-cells that can occur either in sporadic (70–80%) or hereditary (20–30%) form. In this study we aimed to identify recurrent copy number alterations (CNA) that might be related to the pathogenesis or progression of MTC. We used Affymetrix SNP array 6.0 on MTC and paired-blood samples to identify CNA using PennCNV and Genotyping Console software. The algorithms identified recurrent copy number gains in chromosomes 15q, 10q, 14q and 22q in MTC, whereas 4q cumulated losses. Coding genes were identified within CNA regions. The quantitative PCR analysis performed in an independent series of MTCs (<i>n</i> = 51) confirmed focal recurrent copy number gains encompassing the <i>DLK1</i> (14q32.2) and <i>AIFM3</i> (22q11.21) genes. Immunohistochemistry confirmed AIFM3 and DLK1 expression in MTC cases, while no expression was found in normal thyroid tissues and few MTC samples were found with normal copy numbers. The functional relevance of CNA was also assessed by in silico analysis. CNA status correlated with protein expression (<i>DLK1</i>, <i>p</i> = 0.01), tumor size (<i>DLK1</i>, <i>p</i> = 0.04) and AJCC staging (<i>AIFM3</i><i>p</i> = 0.01 and <i>DLK1</i><i>p</i> = 0.05). These data provide a novel insight into MTC biology, and suggest a common CNA landscape, regardless of if it is sporadic or hereditary MTC. |
| first_indexed | 2024-03-09T05:27:20Z |
| format | Article |
| id | doaj.art-6fa76e1dc3484cbe8695ade88426aba4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T05:27:20Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6fa76e1dc3484cbe8695ade88426aba42023-12-03T12:35:16ZengMDPI AGCancers2072-66942021-01-0113221810.3390/cancers13020218Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent <i>AIFM3</i> and <i>DLK1</i> Copy Gain in Medullary Thyroid CarcinomaAline Neves Araujo0Cléber Pinto Camacho1Thais Biude Mendes2Susan Chow Lindsey3Lais Moraes4Marta Miyazawa5Rosana Delcelo6Renata Pellegrino7Diego Robles Mazzotti8Rui Monteiro de Barros Maciel9Janete Maria Cerutti10Genetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 andar, São Paulo 04039-032, BrazilLaboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 andar, São Paulo 04039-032, BrazilGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 andar, São Paulo 04039-032, BrazilLaboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 andar, São Paulo 04039-032, BrazilGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 andar, São Paulo 04039-032, BrazilGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 andar, São Paulo 04039-032, BrazilDepartment of Pathology, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 740, São Paulo 04023-900, BrazilCenter for Applied Genomics, The Children’s Hospital of Philadelphia, Research Institute, 3401 Civic Center Blvd., Philadelphia, PA 191014, USADivision of Sleep Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 191014, USALaboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 andar, São Paulo 04039-032, BrazilGenetic Bases of Thyroid Tumors Laboratory, Division of Genetics, Department of Morphology and Genetics, Escola Paulista de Medicina, Universidade Federal de São Paulo, Pedro de Toledo 669, 11 andar, São Paulo 04039-032, BrazilMedullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid C-cells that can occur either in sporadic (70–80%) or hereditary (20–30%) form. In this study we aimed to identify recurrent copy number alterations (CNA) that might be related to the pathogenesis or progression of MTC. We used Affymetrix SNP array 6.0 on MTC and paired-blood samples to identify CNA using PennCNV and Genotyping Console software. The algorithms identified recurrent copy number gains in chromosomes 15q, 10q, 14q and 22q in MTC, whereas 4q cumulated losses. Coding genes were identified within CNA regions. The quantitative PCR analysis performed in an independent series of MTCs (<i>n</i> = 51) confirmed focal recurrent copy number gains encompassing the <i>DLK1</i> (14q32.2) and <i>AIFM3</i> (22q11.21) genes. Immunohistochemistry confirmed AIFM3 and DLK1 expression in MTC cases, while no expression was found in normal thyroid tissues and few MTC samples were found with normal copy numbers. The functional relevance of CNA was also assessed by in silico analysis. CNA status correlated with protein expression (<i>DLK1</i>, <i>p</i> = 0.01), tumor size (<i>DLK1</i>, <i>p</i> = 0.04) and AJCC staging (<i>AIFM3</i><i>p</i> = 0.01 and <i>DLK1</i><i>p</i> = 0.05). These data provide a novel insight into MTC biology, and suggest a common CNA landscape, regardless of if it is sporadic or hereditary MTC.https://www.mdpi.com/2072-6694/13/2/218medullary thyroid carcinomaRETcopy number alterationAIFM3DLK1 |
| spellingShingle | Aline Neves Araujo Cléber Pinto Camacho Thais Biude Mendes Susan Chow Lindsey Lais Moraes Marta Miyazawa Rosana Delcelo Renata Pellegrino Diego Robles Mazzotti Rui Monteiro de Barros Maciel Janete Maria Cerutti Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent <i>AIFM3</i> and <i>DLK1</i> Copy Gain in Medullary Thyroid Carcinoma Cancers medullary thyroid carcinoma RET copy number alteration AIFM3 DLK1 |
| title | Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent <i>AIFM3</i> and <i>DLK1</i> Copy Gain in Medullary Thyroid Carcinoma |
| title_full | Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent <i>AIFM3</i> and <i>DLK1</i> Copy Gain in Medullary Thyroid Carcinoma |
| title_fullStr | Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent <i>AIFM3</i> and <i>DLK1</i> Copy Gain in Medullary Thyroid Carcinoma |
| title_full_unstemmed | Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent <i>AIFM3</i> and <i>DLK1</i> Copy Gain in Medullary Thyroid Carcinoma |
| title_short | Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent <i>AIFM3</i> and <i>DLK1</i> Copy Gain in Medullary Thyroid Carcinoma |
| title_sort | comprehensive assessment of copy number alterations uncovers recurrent i aifm3 i and i dlk1 i copy gain in medullary thyroid carcinoma |
| topic | medullary thyroid carcinoma RET copy number alteration AIFM3 DLK1 |
| url | https://www.mdpi.com/2072-6694/13/2/218 |
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