| Full text | |
| Author(s): |
Bim, Larissa Valdemarin
[1]
;
Ribeiro Carneiro, Thaise Nayane
[1]
;
Buzatto, Vanessa Candiotti
[2]
;
Colozza-Gama, Gabriel Avelar
[1]
;
Koyama, Fernanda C.
[2]
;
Dias Thomaz, Debora Mota
[1]
;
de Jesus Paniza, Ana Carolina
[1]
;
Lee, Eunjung Alice
[3, 4]
;
Favoretto Galante, Pedro Alexandre
[2]
;
Cerutti, Janete Maria
[1]
Total Authors: 10
|
| Affiliation: | [1] Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Genet Bases Thyroid Tumors Lab, Escola Paulista Me, Pedro Toledo 669, 11 Andar, BR-04039032 Sao Paulo, SP - Brazil
[2] Hosp Sirio Libanes, Ctr Oncol Mol, Rua Prof Daher Cutait 69, BR-01308060 Sao Paulo, SP - Brazil
[3] Boston Childrens Hosp, Div Genet & Genom, 3 Blackfan Circle, Boston, MA 02115 - USA
[4] Harvard Med Sch, 3 Blackfan Circle, Boston, MA 02115 - USA
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | CANCERS; v. 13, n. 20 OCT 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
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.Thyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of follicular thyroid carcinoma (FTC), Hurthle 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. (AU) | |
| FAPESP's process: | 18/23497-1 - Genetic profile identified in thyroid tumors affect tumor cell metabolism? |
| Grantee: | Janete Maria Cerutti |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 14/06570-6 - Comprehensive whole exome, paired-end RNA and genome sequencing: new insights into genetic bases of thyroid carcinoma in pediatric and adult ages and applications in clinical practice |
| Grantee: | Janete Maria Cerutti |
| Support Opportunities: | Research Projects - Thematic Grants |