scholarly journals TERT promoter mutations in thyroid cancer: a report from a Middle Eastern population

2015 ◽  
Vol 22 (6) ◽  
pp. 901-908 ◽  
Author(s):  
Ebtesam Qasem ◽  
Avaniyapuram Kannan Murugan ◽  
Hindi Al-Hindi ◽  
Mingzhao Xing ◽  
Mai Almohanna ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Middle East ◽  
Direct Sequencing ◽  
Tumour Size ◽  
Middle Eastern ◽  
Middle Eastern Population ◽  
Thyroid Adenomas ◽  
Cell Variant ◽  
Hürthle Cell Thyroid Cancer ◽  
Promoter Mutations

Telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have recently been described in follicular cell-derived thyroid cancer (TC) in patients from North America and Europe. In this study, we explored whether these findings could be replicated in patients from a different ethnic group. We screened 17 benign thyroid adenomas and 265 TC samples from patients in the Middle East for these mutations by PCR and direct sequencing using DNA isolated from paraffin-embedded tumor tissues. None of the 17 benign adenomas harbored TERT promoter mutations. Of 265 TC, 34 (12.8%) harbored TERT promoter mutations, including 10/153 (6.5%) conventional papillary TC (CPTC), 8/57 (14.0%) follicular variant PTC, 9/30 (30%) tall cell variant PTC, 1/3 (30%) Hurthle cell thyroid cancer (HTC), 1/5 (20%) follicular TC, and 5/13 (38.5%) poorly differentiated TC. C250T mutation was present in only 6/265 (2.3%) cases, while C228T mutation was present in a total of 28/265 (10.6%) cases. These two mutations were mutually exclusive. TERT promoter mutations were significantly more common in older (≥45 years) than younger patients and were associated with larger tumour size, vascular invasion, higher TNM stage (stage III and IV), BRAFV600E mutation and persistent/recurrent disease at 6–12 months after initial treatment and at the last follow up. These associations were stronger in non-CPTC. Thus, this study on a large cohort of TC patients from Middle East demonstrates that TERT promoter mutations are relatively common, especially in the non-CPTC, and are associated with more aggressive histopathological features, BRAFV600E mutation, and disease persistence/recurrence than the WT TERT.

scholarly journals Telomerase reverse transcriptase promoter mutations in cancers derived from multiple organ sites among middle eastern population

Genomics ◽  
2020 ◽  
Vol 112 (2) ◽  
pp. 1746-1753
Author(s):  
Abdul K. Siraj ◽  
Rong Bu ◽  
Kaleem Iqbal ◽  
Sandeep Kumar Parvathareddy ◽  
Nabil Siraj ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Middle Eastern ◽  
Multiple Organ ◽  
Telomerase Reverse Transcriptase ◽  
Eastern Population ◽  
Middle Eastern Population ◽  
Promoter Mutations

Nasal Allergies in the Middle Eastern Population: Results from the “Allergies in Middle East Survey”

2012 ◽  
Vol 26 (6_suppl) ◽  
pp. S3-S23 ◽  
Author(s):  
Hussain Abdulrahman ◽  
Usamah Hadi ◽  
Hisham Tarraf ◽  
Mohammad Gharagozlou ◽  
Mohamed Kamel ◽  
...  
Keyword(s):  
Middle East ◽  
Middle Eastern ◽  
Eastern Population ◽  
Middle Eastern Population

scholarly journals A Clinical Overview of Telomerase-Associated Aberrancies in Follicular Thyroid Tumors as Diagnostic and Prognostic Markers: Tert Alert!

2019 ◽  
Vol 109 (3) ◽  
pp. 187-192 ◽  
Author(s):  
C. C. Juhlin
Keyword(s):  
Thyroid Cancer ◽  
Reverse Transcriptase ◽  
Malignant Potential ◽  
Telomerase Reverse Transcriptase ◽  
Thyroid Tumors ◽  
Reverse Transcriptase Gene ◽  
Thyroid Carcinomas ◽  
Thyroid Adenomas ◽  
Promoter Mutations ◽  
Follicular Thyroid Tumors

Background and Aims: Endocrine surgeons and pathologists alike are well aware of the diagnostic predicament that follicular thyroid tumors impose in the clinical setting, best exemplified by the current inability to preoperatively assess the malignant potential of each individual lesion. As the proper recognition of a follicular thyroid carcinoma lies in the histopathological identification of invasive behavior, preoperative cytology alone is not yet sufficient to identify malignant tumors eligible for a total thyroidectomy upfront. Numerous auxiliary markers have been proposed as discriminating markers between follicular thyroid carcinomas and follicular thyroid adenomas, although many have proven suboptimal in terms of sensitivity, specificity, or overall clinical practicality. Of late, recurrent promoter mutations in the telomerase reverse transcriptase gene have been intimately coupled to subsets of well-differentiated thyroid cancer specimen with aggressive clinical characteristics as well as less differentiated forms of thyroid cancer with exceedingly poor prognosis. The mutations are thought to enhance the telomerase reverse transcriptase gene expressional output and cause immortalization through telomerase-associated mechanisms. Materials and Methods: In this review, the current value of telomerase reverse transcriptase promoter mutations is detailed from a clinical angle—as well as the possible future application of additional telomerase reverse transcriptase gene aberrations as adjunct markers for the proper recognition of malignant potential. Results: Telomerase reverse transcriptase promoter mutations are found in subsets of follicular thyroid carcinomas and follicular tumors of uncertain malignant potential while exceedingly rare in recurrence-free follicular thyroid adenomas. Collectively, these aberrancies are suggested as possible diagnostic and prognostic discriminators of follicular thyroid tumors. Conclusions: Telomerase reverse transcriptase gene analyses greatly facilitate the clinical assessment of follicular thyroid tumors, and pinpoints cases at risk of future recurrences. High-volume, tertiary thyroid centers are therefore recommended to implement the mutational screening in clinical routine.

scholarly journals POLE and POLD1 pathogenic variants in the proofreading domain in papillary thyroid cancer

2020 ◽  
Vol 9 (9) ◽  
pp. 923-932
Author(s):  
Abdul K Siraj ◽  
Rong Bu ◽  
Maham Arshad ◽  
Kaleem Iqbal ◽  
Sandeep Kumar Parvathareddy ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Middle Eastern ◽  
Stage Iv ◽  
Pathogenic Variant ◽  
Eastern Region ◽  
Papillary Thyroid ◽  
Pathogenic Variants ◽  
Middle Eastern Population ◽  
Low Expression

Thyroid cancer is the most frequent endocrine cancer with an increasing incidence rate worldwide and is the second most common malignancy among females in Saudi Arabia. Papillary thyroid cancer (PTC) is the most common subtype. Germline pathogenic variants in the proofreading domain of the POLE and POLD1 genes predispose to several types of cancers. However, the role of pathogenic variants of these two genes in PTC remains unknown. Capture sequencing, Sanger sequencing and immunohistochemistry were performed on 300 PTC cases from the Middle Eastern region. One germline pathogenic variant each of POLE (1/300, 0.33%) and POLD1 (1/300, 0.33%) genes was identified. Low expression of POLD1 was detected in 46.5% (133/286) of cases and was significantly associated with the follicular variant of PTC (P = 0.0006), distant metastasis (P = 0.0033) and stage IV tumours (P = 0.0081). However, no somatic pathogenic variant was detected in POLE gene. Furthermore, low expression of POLE was noted in 61.7% (175/284) of cases with no significant clinicopathological associations. Our study shows that pathogenic variant in the POLE and POLD1 proofreading domain is a cause of PTC and low expression of POLD1 is associated with poor prognostic markers in the Middle Eastern population. Further studies from different geographic populations are needed to determine the frequency and spectrum of proofreading domain pathogenic variants in POLE and POLD1 genes and in PTC from different ethnicities.

HABP2 Gene Mutations Do Not Cause Familial or Sporadic Non-Medullary Thyroid Cancer in a Highly Inbred Middle Eastern Population

Thyroid ◽  
2016 ◽  
Vol 26 (5) ◽  
pp. 667-671 ◽  
Author(s):  
Ali S. Alzahrani ◽  
Avaniyapuram Kannan Murugan ◽  
Ebtesam Qasem ◽  
Hindi Al-Hindi
Keyword(s):  
Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Middle Eastern ◽  
Gene Mutations ◽  
Eastern Population ◽  
Medullary Thyroid ◽  
Middle Eastern Population
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