However, two gatekeeper mutations V804M and V804L in RET kinase domain have been frequently observed to cause drug resistance during the targeted therapy, largely limiting the application of reversible TKIs in TC.
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.
Potentially druggable kinase fusions involving ALK, ROS, RET, NTRK and FGFR gene families were detected in bladder carcinoma (3.3%), glioblastoma (4.4%), head and neck cancer (1.0%), low-grade glioma (1.5%), lung adenocarcinoma (1.6%), lung squamous cell carcinoma (2.3%) and thyroid carcinoma (8.7%), suggesting a potential for application of kinase inhibitors across tumor types.
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.
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.
Our data indicate that RAF-1 is important for the survival of TPC-1 cells independently of the classical MEK1/2-ERK activation, offering new perspectives on RET/PTC signaling and for the therapy of thyroid cancers.
Twenty-four (27%) of 89 patients were diagnosed with thyroid cancer (50% papillary thyroid carcinoma [PTC], 50% follicular variant of papillary thyroid carcinoma [FVPTC]).
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.
This study confirms the occurrence of synchronous MTC and PTC and is the first evidence of the co-existence of melanoma and distinct thyroid cancers of different origin.
All fusions identified were between RET and KIF5B genes, and no RET fusions to CCDC6 or NCOA4 genes, characteristic for thyroid cancer, were identified in the irradiated lung cells.
The posttest probability of thyroid cancer was 100% for nodules positive for BRAF or RET-PTC, 70% for RAS or PAX8-PPARG, and 88% for molecular cytology overall.
Treatment of the transgenic mice with vandetanib, which is a RET tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration for the treatment of thyroid carcinoma, for 8 or 20 weeks led to a marked reduction in the number of lung tumors (3.3 versus 0 and 6.5 versus 0.2 per tissue section, respectively; P < 0.01, t-test).
In addition, expression of Sin1 and activation of AKT kinase were analyzed in fresh-frozen tissue samples (normal/tumor), primary cell cultures (papillary thyroid carcinoma [PTC]), and an established thyroid cancer cell line (medullary thyroid carcinoma) by Western blotting.
RET, a transmembrane receptor tyrosine kinase and a receptor for the glial cell-derived neurotrophic factor family ligands, was one of the first oncogenes to be identified, and has been shown to be an oncogene in thyroid cancer and pheochromocytoma.
Exons 10, 11, 13, and 16 were sequenced in all, and all exons of RET in 43 of the subjects, including those with thyroid cancer, RET mutations, suspicious clinical findings, and familial or long-segment disease.
EGFR-H was detected in 39.5% of carcinomas (n = 32) from patients with papillary (PTC, 46.2%, n = 18), follicular (29.6%, n = 8), and anaplastic (100.0%, n = 6) but not medullary (0.0%, n = 9) thyroid carcinoma.