Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas.
Additional studies of larger series of M/R and primary TCV should be performed to delineate further any potential application of LOH for chromosome 1 and the p53 gene as a tool for diagnosing TCV with cytologic preparations.Cancer (Cancer Cytopathol)
By selecting PTC-derived cell lines with different genetic backgrounds characteristic of BRAF<sup>V600E</sup> -like PTC subgroups, we demonstrate that thyrosphere cells with BRAF<sup>V600E</sup> and TP53 mutations show shorter telomeres than those harboring RET/PTC or BRAF<sup>V600E</sup> and wild-type TP53.
By simultaneously activating Kras and deleting p53 (Trp53) in thyroid follicular cells, we have generated a novel mouse model that develops papillary thyroid cancer invariably progressing to PDTC.
Compared to the PTC control group, the HPTC patients had larger tumors (30 mm vs. 16 mm; p < 0.001), more frequent lymph node involvement (68% vs. 38%; p = 0.01), and remote disease (16% vs. 3%; p < 0.0001), a similar prevalence of the BRAF<sup>V600E</sup> mutation (58% vs. 59%), a higher prevalence of TP53 mutations (17% vs. 1%; p < 0.05), and a worse outcome (structural/biochemical disease: 32% vs. 9%; p < 0.0001).
Exclusion of mutations in TP53 and the TERT promoter could be considered as an adjunct tool when assessing papillary thyroid cancer with focal pleomorphism.
Further, many cell lines have lost the expression of thyroid-specific genes and have altered karyotypes, while they exhibit activation of several oncogenes (BRAF, v-raf murine sarcoma viral oncogene homolog B1; RAS, rat sarcoma; and RET/PTC, rearranged in transformation/papillary thyroid carcinoma) and inactivation of tumor suppressor gene (TP53) which is known to be important for thyroid tumorigenesis.
In case of men, AR mRNA showed a positive correlation with AR and cyclin D1 proteins in papillary thyroid carcinoma (PTC); and CBP and Sp1 in follicular thyroid adenoma (FTA), whereas AR mRNA showed a positive correlation with p53.
In the analyses of ATM/TP53 (rs1801516/rs664677/rs609429/rs1042522) combinations, the GG/TC/CG/GC genotype strongly associated with radiation-induced PTC (OR = 2.10, 95% CI 1.17-3.78).
In this review, we briefly summarize the present state of knowledge about miRNA, BRAF and p53 mutation in the development of PTC and the possibility of using detecting BRAF mutation and miRNA expression in liquid biopsy.
Intriguingly, mortalin depletion induced varied effects on cell cycle arrest (G0/G1 phase arrest in TPC-1 and C643, G2/M phase arrest in 8505C, and mild G2/M phase arrest with increased sub-G0/G1 population in FTC133) and on the levels of TP53, E2F-1, p21<sup>CIP1</sup>, p27<sup>KIP1</sup>, and poly (ADP-ribose) polymerase cleavage in these cells, suggesting that thyroid tumor cells respond to mortalin depletion in a cell type-specific manner.
LOH analysis showed that the PTC retained chromosome arm 17p (where the p53 gene resides), whereas the carcinoma was associated with the loss of this allele.
Mutations in p53 exons 6 and 7 have been reported in the childhood papillary thyroid carcinomas in Belarus presumably as a result of radioiodine fall-out.
Mutations in the p53 tumour-suppressor gene (exons 5-8) were investigated in 31 Belarussian childhood thyroid tumours (24 cases of papillary thyroid carcinoma, 3 benign tumours and 2 cases each of thyroiditis and goiter); 33 thyroid tumours from juveniles and adults without radiation exposures (25 carcinomas of various histological types, including 11 papillary carcinomas and 8 adenomas) and 6 tumours from adults (4 papillary carcinomas, 1 adenoma, 1 goiter) served as controls.
Nuclear accumulation of immunoreactive p53 protein is associated with two established indicators of poor prognosis in papillary carcinoma of the thyroid.
RASSF10 is Epigenetically Inactivated and Suppresses Cell Proliferation and Induces Cell Apoptosis by Activating the p53 Signalling Pathway in Papillary Thyroid Carcinoma Cancer.