Non-Coding RNAs: Uncharted Mediators of Thyroid Cancer Pathogenesis.

Thyroid cancer is the most prevalent malignancy of the endocrine system and the ninth most common cancer globally. Despite the advances in the management of thyroid cancer, there are critical issues with the diagnosis and treatment of thyroid cancer that result in the poor overall survival of undifferentiated and metastatic thyroid cancer patients. Recent studies have revealed the role of different non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) that are dysregulated during thyroid cancer development or the acquisition of resistance to therapeutics, and may play key roles in treatment failure and poor prognosis of the thyroid cancer patients. Here, we systematically review the emerging roles and molecular mechanisms of ncRNAs that regulate thyroid tumorigenesis and drug response. We then propose the potential clinical implications of ncRNAs as novel diagnostic and prognostic biomarkers for thyroid cancer.

Familial non-medullary thyroid cancer: unraveling the genetic maze.

Familial non-medullary thyroid cancer (FNMTC) constitutes 3-9% of all thyroid cancers. Out of all FNMTC cases, only 5% in the syndromic form has well-studied driver germline mutations. These associated syndromes include Cowden syndrome, familial adenomatous polyposis, Gardner syndrome, Carney complex type 1, Werner syndrome and DICER1 syndrome. It is important for the clinician to recognize these phenotypes so that genetic counseling and testing can be initiated to enable surveillance for associated malignancies and genetic testing of family members. The susceptibility chromosomal loci and genes of 95% of FNMTC cases remain to be characterized. To date, 4 susceptibility genes have been identified (SRGAP1 gene (12q14), TITF-1/NKX2.1 gene (14q13), FOXE1 gene (9q22.33) and HABP2 gene (10q25.3)), out of which only the FOXE1 and the HABP2 genes have been validated by separate study groups. The causal genes located at the other 7 FNMTC-associated chromosomal loci (TCO (19q13.2), fPTC/ PRN (1q21), FTEN (8p23.1-p22), NMTC1 (2q21), MNG1 (14q32), 6q22, 8q24) have yet to be identified. Increasingly, gene regulatory mechanisms (miRNA and enhancer elements) are recognized to affect gene expression and FNMTC tumorigenesis. With newer sequencing technique, along with functional studies, there has been progress in the understanding of the genetic basis of FNMTC. In our review, we summarize the FNMTC studies to date and provide an update on the recently reported susceptibility genes including novel germline SEC23B variant in Cowden syndrome, SRGAP1 gene, FOXE1 gene and HABP2 genes in non-syndromic FNMTC.

Frequent screening with serial neck ultrasound is more likely to identify false-positive abnormalities than clinically significant disease in the surveillance of intermediate risk papillary thyroid cancer patients without suspicious findings on follow-up ultrasound evaluation.

CONTEXT: American Thyroid Association (ATA) intermediate-risk thyroid cancer patients who achieve an excellent treatment response demonstrate a low risk of structural disease recurrence. Despite this fact, most patients undergo frequent surveillance neck ultrasound (US) during follow-up. OBJECTIVE: The objective of the study was to evaluate the clinical utility of routine screening neck US in ATA intermediate-risk patients documented to have a nonstimulated thyroglobulin less than 1.0 ng/mL and a neck US without suspicious findings after therapy. PATIENTS AND DESIGN: Retrospective review of 90 ATA intermediate-risk papillary thyroid carcinoma patients treated with total thyroidectomy and radioactive iodine ablation in a tertiary referral center. MAIN OUTCOME MEASURES: A comparison between the frequency of finding false-positive US abnormalities and the frequency of identifying structural disease recurrence in the study cohort was measured. RESULTS: Over a median of 10 years, 90 patients had a median of six US (range 2-16). Structural disease recurrence was identified in 10% (9 of 90) at a median of 6.3 years. Recurrence was associated with other clinical indicators of disease in 5 of the 90 patients (5.6%, 5 of 90) and was detected without other signs of recurrence in four patients (4.8%, 4 of 84). False-positive US abnormalities were identified in 57% (51 of 90), leading to additional testing, which failed to identify clinically significant disease. CONCLUSIONS: In ATA intermediate-risk patients who have a nonstimulated thyroglobulin less than 1.0 ng/mL and a neck US without suspicious findings after therapy, frequent US screening during follow-up is more likely to identify false-positive abnormalities than clinically significant structural disease recurrence.