Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma
| Autor: | Susan C. Lindsey, Rosana Delcelo, Renata Pellegrino, Aline Neves Araujo, Cleber P. Camacho, Diego R. Mazzotti, Lais Moraes, Janete M. Cerutti, Thais Biude Mendes, Rui M. B. Maciel, Marta Miyazawa |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research endocrine system copy number alteration endocrine system diseases Biology lcsh:RC254-282 Pathogenesis Thyroid carcinoma 03 medical and health sciences 0302 clinical medicine medullary thyroid carcinoma medicine Genotyping Gene AIFM3 DLK1 Thyroid fungi food and beverages lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Immunohistochemistry RET SNP array |
| Zdroj: | Cancers, Vol 13, Iss 218, p 218 (2021) Cancers Volume 13 Issue 2 |
| ISSN: | 2072-6694 |
| Popis: | Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid C-cells that can occur either in sporadic (70&ndash 80%) or hereditary (20&ndash 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 (n = 51) confirmed focal recurrent copy number gains encompassing the DLK1 (14q32.2) and AIFM3 (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 (DLK1, p = 0.01), tumor size (DLK1, p = 0.04) and AJCC staging (AIFM3p = 0.01 and DLK1p = 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. |
| Databáze: | OpenAIRE |
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