Effect of Interferon-γ on the Basal and the TNFα-Stimulated Secretion of CXCL8 in Thyroid Cancer Cell Lines Bearing Either the RET/PTC Rearrangement Or the BRAF V600e Mutation.
We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer.
We investigated the role of PD-L1 in thyroid cancer with respect to BRAF mutation and MAP kinase pathway activity and the effect of anti PD-L1 antibody therapy on tumor regression and intra-tumoral immune response alone or in combination with BRAF inhibitor (BRAFi).
In this study, we investigated the relationship between the TME and thyroid cancer progression in a mouse model where thyroid-specific expression of oncogenic BRAF and loss of Pten (Braf(V600E)/Pten(-/-)/TPO-Cre) leads to papillary thyroid cancers (PTC) that rapidly progress to poorly differentiated thyroid cancer (PDTC).
Triple combination of PLX4032, SAHA, and TSH is a specific robust regimen to restore RAI avidity in RAI-refractory BRAFV600E-positive thyroid cancer, which warrants clinical trials to confirm.
We have identified previously undiscovered BRAF in-frame deletions near the αC-helix region of the kinase domain in pancreatic, lung, ovarian, and thyroid cancers.
As a result of BRAF kinase inhibition, reduction in MEK kinase activity was seen (p < 0.05) in both thyroid cancer cell lines (72 and 75 %, respectively).
BRAF fusions included 3% (14/531) of melanomas; 2% (15/701) of gliomas; 1.0% (3/294) of thyroid cancers; 0.3% (3/1,062) pancreatic carcinomas; 0.2% (8/4,013) nonsmall-cell lung cancers and 0.2% (4/2,154) of colorectal cancers, and were enriched in pilocytic (30%) vs. nonpilocytic gliomas (1%; p < 0.0001), Spitzoid (75%) vs. nonSpitzoid melanomas (1%; p = 0.0001), acinar (67%) vs. nonacinar pancreatic cancers (<1%; p < 0.0001) and papillary (3%) vs. nonpapillary thyroid cancers (0%; p < 0.03).
While the majority of seminomas retain a hypo-methylated genome, a small fraction displays a highly methylated genome, resembling hyper-methylated non-seminomas.It is well established from e.g. melanoma, colorectal and thyroid cancer that a methylated phenotype can be correlated to prognosis and can be related to BRAF mutations.
Evidence has also shown that the detection of the BRAF(V600E) mutation in cancer is crucial in order to identify novel avenues for thyroid cancer treatment.Based on the BRAF kinase structure, novel drugs can potentially be designed to target oncogenic BRAF in cancer therapeutics.
Here, we firstly find CNTN1 is a new gene which can be regulated by RET/PTC3 (Ret proto-oncogene and Ret-activating protein ELE1) rearrangement gene and the protein level of CNTN1 is increasing in thyroid cancer.
Somatic mutations in established thyroid cancer genes were detected in 14 of 22 (64%) tumors and included recurrent mutations in BRAF, TP53 and RAS-family genes (6 cases each), as well as PIK3CA (2 cases) and single cases of CDKN1B, CDKN2C, CTNNB1 and RET mutations.
Twenty-four (27%) of 89 patients were diagnosed with thyroid cancer (50% papillary thyroid carcinoma [PTC], 50% follicular variant of papillary thyroid carcinoma [FVPTC]).
BRAF(V600E) mutation analysis is superior to RAS point mutations and evaluation of RET/PTC rearrangements in the diagnosis of thyroid cancer, even in indeterminate lesions.
The usefulness of BRAF testing is limited by the low rate of BRAF-positive cases in other categories, thereby highlighting the need to identify other genetic drivers of clinically aggressive thyroid cancers.
BRAF(V600E) mutation analysis is superior to RAS point mutations and evaluation of RET/PTC rearrangements in the diagnosis of thyroid cancer, even in indeterminate lesions.
Rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, BRAF (B-RAF proto-oncogene, serine/threonine kinase) gene mutations, RAS (rat sarcoma) mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways playing a crucial role in the development of thyroid cancer.