New Insights in Thyroid Cancer and p53 Family Proteins

Abstract

Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured by surgery and radioiodine, unlike undifferentiated tumors that fail to uptake radioactive iodine and are usually resistant to chemotherapy. Therefore, novel and more effective therapies for these aggressive neoplasias are urgently needed. Whereas most genetic events underlying the pathogenesis of well-differentiated thyroid cancers have been identified, the molecular mechanisms that generate undifferentiated thyroid carcinomas are still unclear. To date, one of the best-characterized genetic alterations leading to the development of poorly differentiated thyroid tumors is the loss of the p53 tumor suppressor gene. In addition, the existence of a complex network among p53 family members (p63 and p73) and their interactions with other factors that promote thyroid cancer progression has been well documented. In this review, we provide an update on the current knowledge of the role of p53 family proteins in thyroid cancer and their possible use as a therapeutic target for the treatment of the most aggressive variants of this disease.

TP53 Mutations in Serum Circulating Cell-Free Tumor DNA As Longitudinal Biomarker for High-Grade Serous Ovarian Cancer

“…The tumor suppressor TP53 gene is mainly mutated in exons 4-9, encoding for the DNA-binding domain of the protein [21]. It has been demonstrated that the aberrant protein is able to influence tumor progression toward migration, invasion, and metastasis in different tumor types [22][23][24][25][26]. In our study, 85% of patients harbored non-functional TP53 alterations in tumor tissue, which is in keeping with previous studies reporting TP53 mutations in more than 80% of HGSOC [27][28][29].…”

Probability-based detection of phosphoproteomic uncertainty reveals rare signaling events driven by oncogenic kinase gene fusion

“…In particular, we noted that in cells expressing the PRKAR1A-RET fusion there was enrichment for signaling via PI3K-AKT-mTOR, which has previously been shown to affect cell proliferation, viability and iodide uptake in thyroid cells 9 , and Myc, which is known to be involved in the majority of human cancers and leads to the acquisition of hallmark cancer characteristics such as uncontrolled proliferation 10 . Interestingly we observed that additional signaling pathways were modulated in the colonies expressing PRKAR1A-RET, including P53, alterations in which are known to contribute to carcinogenesis in thyroid tissue 11 . Given the significant number of additional phosphorylation sites quantified by the Monte Carlo model (most likely due to the sparcity of the data, which has fewer biological replicates than the other analyzed datasets) we used DAVID 12 to determine whether there was enrichment of specific signaling pathways which were only quantified by Monte Carlo analysis.…”

Prognostic importance of immunologochemical markers of papillary thyroid cancer

“…Це наше припущення підтверджується дослідженням Tang J. та співавт. (2017), що не знаходять різниці між показниками безрецидивного виживання навіть для інтратиреоїдних пухлин розмірами до 4 см без ознак агресивного перебігу [9]. Згідно нашого клінічного досвіду використання гемітиреоїдектомії можливо при розмірі інтратиреоїдної пухлини розміром до 2 см без ознак інвазії та факторів ризику [10].…”