Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers
Thyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of follicular thyroid carcinoma (FTC), Hürthle cell carcinoma (HCC), and follicular variant of papillary thyroid carcinoma (FVPTC) and their benign counterparts is a challenge for preoperative diagnosis. Nearl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/20/5184 |
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| author | Larissa Valdemarin Bim Thaise Nayane Ribeiro Carneiro Vanessa Candiotti Buzatto Gabriel Avelar Colozza-Gama Fernanda C. Koyama Debora Mota Dias Thomaz Ana Carolina de Jesus Paniza Eunjung Alice Lee Pedro Alexandre Favoretto Galante Janete Maria Cerutti |
| author_facet | Larissa Valdemarin Bim Thaise Nayane Ribeiro Carneiro Vanessa Candiotti Buzatto Gabriel Avelar Colozza-Gama Fernanda C. Koyama Debora Mota Dias Thomaz Ana Carolina de Jesus Paniza Eunjung Alice Lee Pedro Alexandre Favoretto Galante Janete Maria Cerutti |
| author_sort | Larissa Valdemarin Bim |
| collection | DOAJ |
| description | Thyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of follicular thyroid carcinoma (FTC), Hürthle cell carcinoma (HCC), and follicular variant of papillary thyroid carcinoma (FVPTC) and their benign counterparts is a challenge for preoperative diagnosis. Nearly 20–30% of biopsied thyroid nodules are classified as having indeterminate risk of malignancy and incur costs to the health care system. Based on that, 120 patients were screened for the main driver mutations previously described in thyroid cancer. Subsequently, 14 mutation-negative cases that are the main source of diagnostic errors (FTC, HCC, or FVPTC) underwent RNA-Sequencing analysis. Somatic variants in candidate driver genes (<i>ECD, NUP98,</i><i>LRP1B, NCOR1, ATM, SOS1</i>, and <i>SPOP</i>) and fusions were described. <i>NCOR1</i> and <i>SPOP</i> variants underwent validation. Moreover, expression profiling of driver-negative samples was compared to 16 BRAF V600E, <i>RAS</i>, or <i>PAX8-PPARg</i> positive samples. Negative samples were separated in two clusters, following the expression pattern of the <i>RAS/PAX8-PPARg</i> or BRAF V600E positive samples. Both negative groups showed distinct BRS, ERK, and TDS scores, tumor mutation burden, signaling pathways and immune cell profile. Altogether, here we report novel gene variants and describe cancer-related pathways that might impact preoperative diagnosis and provide insights into thyroid tumor biology. |
| first_indexed | 2024-03-10T06:40:22Z |
| format | Article |
| id | doaj.art-4dc0c987216b4d9c86c4cd220f1ea118 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T06:40:22Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4dc0c987216b4d9c86c4cd220f1ea1182023-11-22T17:41:39ZengMDPI AGCancers2072-66942021-10-011320518410.3390/cancers13205184Molecular Signature Expands the Landscape of Driver Negative Thyroid CancersLarissa Valdemarin Bim0Thaise Nayane Ribeiro Carneiro1Vanessa Candiotti Buzatto2Gabriel Avelar Colozza-Gama3Fernanda C. Koyama4Debora Mota Dias Thomaz5Ana Carolina de Jesus Paniza6Eunjung Alice Lee7Pedro Alexandre Favoretto Galante8Janete Maria Cerutti9Genetic 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, SP, 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, SP, BrazilCentro de Oncologia Molecular, Hospital Sírio-Libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo 01308-060, SP, 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, SP, BrazilCentro de Oncologia Molecular, Hospital Sírio-Libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo 01308-060, SP, 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, SP, 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, SP, BrazilDivision of Genetics and Genomics, Boston Children’s Hospital and Harvard Medical School, 3 Blackfan Circle, Boston, MA 02115, USACentro de Oncologia Molecular, Hospital Sírio-Libanês, Rua Professor Daher Cutait 69, Bela Vista, São Paulo 01308-060, SP, 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, SP, BrazilThyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of follicular thyroid carcinoma (FTC), Hürthle cell carcinoma (HCC), and follicular variant of papillary thyroid carcinoma (FVPTC) and their benign counterparts is a challenge for preoperative diagnosis. Nearly 20–30% of biopsied thyroid nodules are classified as having indeterminate risk of malignancy and incur costs to the health care system. Based on that, 120 patients were screened for the main driver mutations previously described in thyroid cancer. Subsequently, 14 mutation-negative cases that are the main source of diagnostic errors (FTC, HCC, or FVPTC) underwent RNA-Sequencing analysis. Somatic variants in candidate driver genes (<i>ECD, NUP98,</i><i>LRP1B, NCOR1, ATM, SOS1</i>, and <i>SPOP</i>) and fusions were described. <i>NCOR1</i> and <i>SPOP</i> variants underwent validation. Moreover, expression profiling of driver-negative samples was compared to 16 BRAF V600E, <i>RAS</i>, or <i>PAX8-PPARg</i> positive samples. Negative samples were separated in two clusters, following the expression pattern of the <i>RAS/PAX8-PPARg</i> or BRAF V600E positive samples. Both negative groups showed distinct BRS, ERK, and TDS scores, tumor mutation burden, signaling pathways and immune cell profile. Altogether, here we report novel gene variants and describe cancer-related pathways that might impact preoperative diagnosis and provide insights into thyroid tumor biology.https://www.mdpi.com/2072-6694/13/20/5184thyroid carcinomaFTCFVPTCHCCNRASBRAF |
| spellingShingle | Larissa Valdemarin Bim Thaise Nayane Ribeiro Carneiro Vanessa Candiotti Buzatto Gabriel Avelar Colozza-Gama Fernanda C. Koyama Debora Mota Dias Thomaz Ana Carolina de Jesus Paniza Eunjung Alice Lee Pedro Alexandre Favoretto Galante Janete Maria Cerutti Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers Cancers thyroid carcinoma FTC FVPTC HCC NRAS BRAF |
| title | Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers |
| title_full | Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers |
| title_fullStr | Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers |
| title_full_unstemmed | Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers |
| title_short | Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers |
| title_sort | molecular signature expands the landscape of driver negative thyroid cancers |
| topic | thyroid carcinoma FTC FVPTC HCC NRAS BRAF |
| url | https://www.mdpi.com/2072-6694/13/20/5184 |
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