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Article type: Research Article
Authors: Zhou, Da-Leia; 1 | Liu, Qinga; 1 | Xu, Bo-Henga; 1 | Li, Yuea | Su, Xuanb | Ye, Zu-Lua | Zhang, Xiaoa | Peng, Jun-Linga | Deng, Linga | Tang, Taoa | Shao, Qionga | Ma, Jiang-Juna | Yang, Xin-Huaa; * | He, Cai-Yuna; *
Affiliations: [a] Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China | [b] Department of Head and Neck, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
Correspondence: [*] Corresponding authors: Xin-Hua Yang and Cai-Yun He, Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, China. Tel.: +86 20 8734 5669/+86 20 8734 5687; E-mails: yangxh@sysucc.org.cn and hecy@sysucc.org.cn.
Note: [1] Da-Lei Zhou, Qing Liu and Bo-Heng Xu contributed equally to the manuscript.
Abstract: The long non-coding RNA (lncRNA) GAS8-AS1 is the second-most frequently altered gene, following the BRAF gene, in papillary thyroid carcinoma (PTC). We aimed to study the specificity and significance of genetic alterations in GAS8-AS1 in PTC. In this study, we reported the prevalence of genetic alterations of GAS8-AS1 in tissues of 48 nodular goiter, 573 papillary thyroid cancer, 95 colorectal cancer, 101 non-small cell lung cancer, 92 glioma, and 69 gastrointestinal stromal tumor patients, and in peripheral white blood cells of 286 healthy volunteers. We observed that the genomic sequence of GAS8-AS1 had a high frequency of genetic alterations in addition to the previously reported c.713A>G/714T>C substitution. Substitution of c.713A>G was completely linked with four other loci at c.714T>C, c.728A>G, c.737G>A, and c.752G>A. Two novel substitutions at c.749G>A and c.826A>G were also found. Interestingly, evidence from different samples indicated that these variations were not unique variants for PTC; they were also found in other malignant tissues and white blood cells of healthy volunteers. The c.713A>G substitution was associated with the T stage of PTC, while c.749G>A was more likely to occur in younger patients with PTC. PTC patients carrying heterozygous variants at the c.749 and c.826 loci had a higher risk of developing multiple lesions. These associations were also observed in patients with PTC and concomitant benign thyroid disease. Notably, the rare homozygous GG at the c.826 site conferred a higher risk of developing T2 PTC without benign thyroid disease, and a lower risk of developing T2 PTC with benign thyroid disease. Alterations of c.749G>A and c.826A>G had higher levels of serum TSH (thyroid stimulating hormone) in PTC subjects. Our study provides evidence that the detection of GAS8-AS1 genetic alterations would be useful in diagnostic screening and prognostic assessment of PTC.
Keywords: Papillary thyroid carcinoma, thyroid function, genetic variation, lncRNA
DOI: 10.3233/CBM-191071
Journal: Cancer Biomarkers, vol. 29, no. 2, pp. 255-264, 2020
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