Classical V600E and other non-hotspot BRAF mutations in adult differentiated thyroid cancer

Most data on differentiated thyroid cancer (DTC) came from the Western world. We describe its salient characteristics and outcome from a Middle Eastern country. Patients and Methods. We studied all cases of TC seen during a 2-year period (2004-2005) seen at our institution. Results. A total of 600 consecutive cases of DTC with a median age at diagnosis of 39 years (5–85) and the female : male ratio of 459 : 141 (76.5% : 23.5%). The cases included classical papillary thyroid cancer (PTC) in 77%, follicular variant PTC in 13.3%, follicular thyroid cancer in 3.2%, and other rare subtypes 6.5%. Total or near-total thyroidectomy was performed in 93%, central and/or lateral neck dissection in 64.5% of cases, and radioactive iodine ablation in 82% of cases. Additional therapies were administered to 154 patients (25.7%). At a median follow-up period of 7.63 years (0.22–13.1), 318 patients (53.3%) were in excellent response, 147 (24.5%) having an indeterminate response, 55 (9.2%) biochemically incomplete, 33 (5.5%) structurally incomplete, and 27 (4.5%) unclassifiable. Twenty cases died secondary to DTC (disease-specific mortality 3.3%). Conclusions. In Saudi Arabia, DTC is common and occurs at young age and predominantly in females. Although remission is common, persistent disease is also common but disease-specific mortality is low.

Thyroid cancer continues to be the most common malignancy of endocrine glands. The incidence of thyroid cancer has risen significantly over the past 4 decades and has emerged as a major health issue. In recent years, significant progress has been achieved in our understanding of the molecular mechanisms of thyroid carcinogenesis, resulting in significant diagnostic, prognostic and therapeutic implications; yet, it has not reached a satisfactory level. Identifying novel molecular therapeutic targets and molecules for diagnosis and prognosis is expected to advance the overall management of this common malignancy. Long noncoding RNAs (lncRNAs) are implicated in the regulation of various key cellular genes involved in cell differentiation, proliferation, cell cycle, apoptosis, migration and invasion mainly through modulation of gene expression. Recent studies have established that lncRNAs are deregulated in thyroid cancer. In this review, we discuss extensively the tumor-suppressive (for example, LINC00271, MEG3, NAMA, PTCSC1/2/3, etc.) and oncogenic (for example, ANRIL, FAL1, H19, PVT1, etc.) roles of various lncRNAs and their possible disease associations implicated in thyroid carcinogenesis. We briefly summarize the strategies and mechanisms of lncRNA-targeting agents. We also describe the potential role of lncRNAs as prospective novel therapeutic targets, and diagnostic and prognostic markers in thyroid cancer.

Gangliogliomas (WHO grade I) are rare tumors affecting the central nervous system and are most frequently observed in children. Next-generation sequencing of tumors is being utilized at an increasing rate in both research and clinical settings to characterize the genetic factors that drive tumorigenesis. Here, we report a rare BRAF somatic mutation (NM_004333.4:c.1794_1796dupTAC; p.Thr599dup) in the tumor genome from a pediatric patient in her late teens, who was initially diagnosed with low-grade ganglioglioma at age 13. This duplication of 3 nt introduces a second threonine residue at amino acid 599 of the BRAF protein. Based on previous studies, this variant is likely to increase kinase activity, similar to the well-characterized BRAF p.Val600Glu (V600E) pathogenic variant. In addition, although the p.T599dup somatic mutation has been documented rarely in human cancers, the variant has not been previously reported in ganglioglioma. The identification of this variant presents an opportunity to consider targeted therapy (e.g., BRAF inhibitor) for this patient.