Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers
| العنوان: | Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers |
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| المؤلفون: | Vanessa Buzatto, Eunjung Lee, Gabriel Avelar Colozza-Gama, Pedro Alexandre Favoretto Galante, Janete M. Cerutti, Debora Mota Dias Thomaz, Larissa V. Bim, Fernanda C. Koyama, Ana Carolina de Jesus Paniza, Thaise Nayane Ribeiro Carneiro |
| المصدر: | Cancers, Vol 13, Iss 5184, p 5184 (2021) Cancers Volume 13 Issue 20 |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Neuroblastoma RAS viral oncogene homolog, Thyroid nodules, Cancer Research, endocrine system diseases, NRAS, SPOP, Malignancy, Article, ECD, BRAF, Thyroid carcinoma, Medicine, HCC, Thyroid cancer, RC254-282, business.industry, NCOR1, Thyroid, FTC, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, thyroid carcinoma, expression profile, Gene expression profiling, medicine.anatomical_structure, Oncology, FVPTC, Cancer research, NUP98, business |
| الوصف: | Simple Summary Thyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of certain malignant thyroid tumors and their benign counterparts is a challenge for preoperative diagnosis, as nearly 20–30% of biopsied thyroid nodules are classified as having an indeterminate risk of malignancy. Although multigene panels customized for thyroid cancer include most of the known tumor driver genes, many thyroid samples have negative results for the tested genes. To expand our knowledge, driver-negative samples were profiled by RNA-sequencing. Here, we report novel gene variants that might be associated with the pathogenesis of thyroid tumors, and show that driver-negative samples have two distinct expression signatures. We believe that our findings will ultimately impact preoperative diagnosis on thyroid nodules and provide directions for further experimental validation analysis. Abstract 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 (ECD, NUP98, LRP1B, NCOR1, ATM, SOS1, and SPOP) and fusions were described. NCOR1 and SPOP variants underwent validation. Moreover, expression profiling of driver-negative samples was compared to 16 BRAF V600E, RAS, or PAX8-PPARg positive samples. Negative samples were separated in two clusters, following the expression pattern of the RAS/PAX8-PPARg 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. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6694 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f335f34f79dc0d3da8d9df5c77cf4eb4 https://doi.org/10.3390/cancers13205184 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f335f34f79dc0d3da8d9df5c77cf4eb4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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