胶质瘤中端粒酶逆转录酶启动子区突变分析及其预后意义

doi:10.3969/j.issn.1004-616x.2015.05.007

Abstract

Abstract:

OBJECTIVE: To explore the correlation between TERT promoter mutations and clinicopathological features in patients with gliomas. METHODS:TERT promoter mutations were screened by direct DNA sequencing in a population-based collection of 78 glioma tissues. The correlation of TERT promoter mutations and the prognosis was analyzed. RESULTS:We identified TERT promoter mutations in 32.1% gliomas, including 28.0% in low grade tumors and 34.0% in high grade tumors. The mutations were much more common in oligoastrocytomas (57.1%) and glioblastomas (44.4%), while much less prevalent in astrocytomas (28.6%) and oligodendrogliomas(23.1%). Median overall survival of the patients harboring mutations in TERT promoter was longer than that without the mutations (P=0.001) in both low (P=0.019) and high grade gliomas (P=0.018). Multivariate analysis revealed TERT promoter mutations and no postoperative adjuvant therapy as significant prognostic factors for shorter survival (P=0.002, HR=3.486, 95%CI: 1.591-7.637;P=0.004, HR=0.331, 95%CI:0.156-0.699). CONCLUSION:TERT promoter mutations frequently occurred in gliomas, which was a prognostic factor of poor outcome for the patients with the same pathological grade gliomas.

Key words: gliomas, telomerase reverse transcriptase, promoter mutations, prognosis

CLC Number:

R739.41

HE Jie, WAN Jinghai, LI Xueji, QIAN Haipeng, MENG Xiaoli, HAO Jiajie, XU Xin, WANG Mingrong. TERT promoter mutation is a potential biomarker for predicting poor outcome in gliomas[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2015, 27(5): 361-365.

References

[1] Ohgaki H. Epidemiology of brain tumors[J]. Methods Mol Biol,2009,472:323-342.

[2] Louis DN,Ohgaki H,Wiestler OD,et al. The 2007 WHO classification of tumours of the central nervous system[J]. Acta Neuropathol,2007,114(2):97-109.

[3] Killela PJ,Pirozzi CJ,Healy P,et al. Mutations in IDH1, IDH2,and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas[J]. Oncotarget,2014, 5(6):1515-1525.

[4] 李剑敏,万丽,黄卡特. 原发性与继发性胶质母细胞瘤中MGMT与突变型P53蛋白表达的差异及其生物学意义[J]. 癌变·畸变·突变,2009,(2):135-140.

[5] Huang FW,Hodis E,Xu MJ,et al. Highly recurrent TERT promoter mutations in human melanoma[J]. Science,2013, 339(6122):957-959.

[6] Horn S,Figl A,Rachakonda PS,et al. TERT promoter mutations in familial and sporadic melanoma[J]. Science, 2013,339(6122):959-961.

[7] Killela PJ,Reitman ZJ,Jiao Y,et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal[J]. PNAS, 2013,110(15):6021-6026.

[8] Liu X,Bishop J,Shan Y,et al. Highly prevalent TERT promoter mutations in aggressive thyroid cancers[J]. Endocr Relat Cancer,2013,20(4):603-610.

[9] Rachakonda PS,Hosen I,de Verdier PJ,et al. TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism [J]. PNAS,2013,110(43):17426-17431.

[10] Koelsche C,Sahm F,Capper D,et al. Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system[J]. Acta Neuropathol,2013,126(6):907-915.

[11] Nonoguchi N,Ohta T,Oh JE,et al. TERT promoter mutations in primary and secondary glioblastomas[J]. Acta Neuropathol, 2013,126(6):931-937.

[12] Bojesen SE,Pooley KA,Johnatty SE,et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer[J]. Nat Genet,2013,45(4):371-384.

[13] Reitman ZJ,Pirozzi CJ,Yan H. Promoting a new brain tumor mutation:TERT promoter mutations in CNS tumors[J]. Acta Neuropathol,2013,126(6):789-792.

[14] Arita H,Narita Y,Fukushima S,et al. Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss[J]. Acta Neuropathol,2013,126(2):267-276.

[1]	PENG Youbin, LIN Hao, LI Ming, HUANG Haihua. Expression of TPX2 and its clinicalsignificance in non-muscle-invasive bladder cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(1): 30-34.
[2]	JIAO Wenpeng, HOU Lin, CUI Meijuan, JIAO Wenjing, MA Ming, ZHANG Jinyan. Expression of miR-93-5p and miR-106b-5p in alcohol-related liver cancer and its clinical significance [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(6): 430-434.
[3]	GAO Xiaobin, WU Xueliang, WANG Shengjie, SUN Guangyuan, WANG Wenjing, LIANG Feng, ZHAO Yifeng, LIU Zhenxian, ZHANG Yingchun. Expression of TRIM59 and its correlations with clinicopathological features in colorectal cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(6): 446-450.
[4]	JIAO Wenjing, ZHANG Jinyan, MA Ming, GUO Xiujuan, FENG Junhua, SHAO Junguo, JIAO Wenpeng. Expression and clinical significance of MTDH and FoxM1 in hepatocellular carcinomas [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(5): 349-353,359.
[5]	ZHANG Shimin, ZHAO Ruijun. Expression of protein tyrosine phosphatase receptor J in breast cancer tissues and its relationship with clinical prognosis [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 276-279,285.
[6]	LIU Xiaoxia, LI Weixia, LI Zhijia, SU Zhenjun, DUAN Xiaohui, HAN Weiwen, WANG Yunxiao, HE Xiaolei, Lu Linlin, JIA Jinhai. Correlations between glutathione peroxidase in serum and clinicopathological outcomes of advanced non-small cell lung cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 286-290,295.
[7]	ZHANG Yuling, WU Jundong, PANG Dongyue, CHEN Chunfa. Changes of Ki67 expression before and after neoadjuvant chemotherapy as a predictor for therapeutic response and rognosis in breast cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 230-235,245.
[8]	SHI Hailin, HE Tianji, LIU Feng, CAI Menghui, GE Bo. Prognostic value of TCGA-database mutation burden in muscle-invasive bladder cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 430-437,443.
[9]	DING Yawen, JIAO Wenjing, WANG Pengyu, LU Gang, MA Ming. Immunophenotype characteristics of plasma cells and clinical significance in multiple myeloma patients [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(6): 464-468,489.
[10]	SHAO Junguo, JIAO Wenjing, WANG Xuexiao, ZHANG Jinyan, MA Ming. Clinical significance of mi-429 and Bmi-1 mRNA expressions in lung carcinoma tissues [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 369-373.
[11]	Lü Yanping, WU Chuancheng, YANG Shuangfeng, HE Chenzhou, HAN Renjie, YAN Wei, LIU Baoying. Relationship between differentially expressed miRNA-SNPs and prognosis of gastric cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 380-386.
[12]	GUO Xiujuan, DU Yanyan, YAN Xi, ZHAO Xuetao, HAN Lina, WU Yipeng, WANG Xuexiao, MA Ming. Expression and clinical significance of CREB in esophageal squamous cell carcinoma tissues [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 387-390,394.
[13]	YANG Li, ZHANG Mengxian, ZHANG Wei, XIONG Yingyou, CHEN Shiyong, FANG Chengxiang. Data mining to investigate expression and significance of aurora kinase A in esophageal carcinoma [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 221-228.
[14]	CHEN Xiuqiong, MENG Fanqiao, XIONG Hua, WANG Yali, ZHOU Yangmei, TANG Wenhua, ZOU Yanmei. Investigation and evaluation of gastric cancer core genes using bioinformatics [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(4): 308-314.
[15]	GAO Jie, ZHANG Xiao, WEI Chao. Involvement of differentially expressed miRNA in prognosis of pancreatic cancers [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(3): 173-179.

TERT promoter mutation is a potential biomarker for predicting poor outcome in gliomas

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments