These findings in a cellular context relevant to the pathological function of RET oncogenes support the role of Ret oncoproteins as useful targets for therapeutic intervention, and suggest RPI-1 as a promising candidate for preclinical development in the treatment of thyroid tumors expressing RET oncogenes.
These results reveal a novel (V600E)BRAF-induced mechanism in thyroid tumours progression and provides a rationale for using the PLX4720 inhibitor to target (V600E)BRAF signalling to effectively control progression of thyroid cancer.
To attempt to clarify this diagnostic problem, we analyzed the BRAF status of thyroid tumors in a group of patients with follicular variant of papillary thyroid carcinoma (FVPTC) and its correlation with cytomorphological features.
This study analyzed TERT promoter mutations in various thyroid tumors and examined their relationship with clinicopathologic factors and the BRAF(V600E) mutation in PTC cases.
AZD6244 potently inhibited MEK 1/2 activity in thyroid cancer cell lines regardless of BRAF mutation status, as evidenced by reduced ERK phosphorylation.
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.
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 mixed expression of BRAF under varying levels of differentiation may explain, in part, the contradictory studies regarding the impact of BRAF mutations on patient prognosis and also indicates a complex genomic signature for dedifferentiated thyroid cancer.
BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas.