We report a FAP-associated CMVPTC tumor with atypically aggressive features harboring a RAS mutation and review the molecular mechanisms associated with this interesting PTC subtype.
Rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) gene rearrangements are one of the major genetic alterations found in papillary thyroid carcinoma.
We have developed a home-brew tetracolor break-apart probe able to simultaneously identify the 2 most common genetic alterations in differentiated thyroid carcinoma: RET/PTC variants in papillary thyroid carcinoma and PAX8/PPARg fusion and variants in follicular thyroid carcinoma.
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.
Point mutations in the BRAF or RAS genes or rearranged in transformation (RET)/papillary thyroid carcinoma (PTC) gene rearrangements are observed in approximately 70% of papillary cancer cases.
Following identification of RET, it was found that somatic rearrangements of this gene, conventionally designated as RET/PTC, are frequently present in papillary thyroid carcinoma.
We did a comprehensive screen for 548 known and putative fusion genes in 27 samples of thyroid tumors and three positive controls-one thyroid cancer cell line (TPC-1) and two PTCs with known CCDC6-RET (alias RET/PTC1) fusion gene, using this microarray.
German patients (n=253) with DTC (papillary thyroid carcinoma [PTC] and follicular thyroid carcinoma [FTC]) and HC (n=302) were genotyped for polymorphisms within the vitamin D metabolizing enzymes such as 25-hydroxylase (CYP2R1[rs12794714, rs10741657]), 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1[rs10877012, rs4646536]), and 25-hydroxyvitamin D 24-hydrolase (CYP24A1[rs927650, rs2248137, rs2296241]).
The list of putative biological and clinical factors that may influence the PTC gene expression profile is long, but there are sufficient data reported in the literature to link expression profiles with differing pathological variants of PTC.
These structural changes lead to the formation of fusion genes RET-PTC, TRK(-T), and BRAF-AKAP9, which originate as a result of intrachromosomal or interchromosomal rearrangements and are found in papillary thyroid carcinoma.
Each case had a previous fine-needle aspiration diagnosis classified according to the British Thyroid Association Guidelines categorized as inadequate (Thy1) (n = 19), benign (Thy2) (n = 19), follicular lesion and follicular lesion with atypia (Thy3) (n = 109), suspicious of PTC (Thy4) (n = 29), or malignant (Thy5) (n = 11).
Given that XB130 is a thyroid-specific tyrosine kinase substrate, we asked whether it is targeted by RET/PTC, a genetically rearranged, constitutively active, thyroid-specific tyrosine kinase that plays a pathogenic role in papillary thyroid cancer.
Preliminary results from our molecular oncology studies on adult-onset papillary thyroid cancer provide evidence for the induction of RET/PTC rearrangements and BRAF point mutation (both known to be early stage events in adult-onset papillary thyroid cancer) but with a difference: cases associated with the rearrangements were more frequent at high doses, and developed sooner than those with BRAF mutation.
The reduction in miR-146a led to less efficient inhibition of target genes involved in the Toll-like receptor and cytokine signaling pathway (TRAF6, IRAK1), and PTC1 (also known as CCDC6 or H4), a gene frequently rearranged with RET proto-oncogene in PTC.
We report the successful validation of a combined gene expression profiling and tissue microarray approach to papillary thyroid carcinoma (PTC) biomarker identification.
We analyzed the methylation pattern of 17 gene promoters in nine thyroid cancer cell lines and in 38 primary thyroid carcinomas (13 papillary thyroid carcinoma [PTC], 10 follicular thyroid carcinoma [FTC], 9 undifferentiated thyroid carcinoma [UTC], 6 medullary thyroid carcinoma [MTC]), 12 goiters, and 10 follicular adenomas (FA) by methylation- specific polymerase chain reaction (PCR).
Although ret/PTC rearrangements have been identified in both spontaneous and radiation-induced papillary thyroid cancer, they seem more frequent among radiation-associated tumors.