Methylation Status of the Telomerase Reverse Transcriptase Promoter in Parotid Tumours and Adjacent Parotid Gland Tissue: A Pilot Study on the Implications for Recurrence and Development of Malignancy.

IF 2.8 4区 医学 Q2 ONCOLOGY
António Paiva-Correia, Joana Apolónio, Alfons Nadal, José Ricardo Brandão, Nádia Silva, Bianca Machado, Ivan Archilla, Pedro Castelo-Branco, Henrik Hellquist
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Abstract

Background/objectives: The methylation of the hypermethylated oncological region (THOR) of human telomerase reverse transcriptase (hTERT) may forecast tumour aggressiveness. This pilot study aimed to evaluate THOR methylation as a potential biomarker for recurrence/malignant transformation in salivary gland pleomorphic adenomas (PA).

Methods: THOR methylation was assessed by quantitative pyrosequencing in 96 parotid tissue samples (benign and malignant), including non-neoplastic parotid tissue, PA, recurrent PA (rPA), and carcinomas, along with their adjacent tissues. TERT promoter mutations (TPMs) were analysed by Sanger sequencing.

Results: THOR methylation significantly differed across the seven groups. Malignant tissues showed higher THOR methylation than non-neoplastic tissues, whereas benign tumours showed no significant difference from non-neoplastic tissue. THOR methylation in rPA was closer to carcinoma than to normal tissue, similar in rPA and tissues adjacent to rPA, and higher in tissues adjacent to carcinomas than in non-neoplastic tissues. A subset of PA-adjacent tissues showed epigenetic alterations, suggesting an increased risk of recurrence or malignant transformation (5-15%). No TPMs were detected.

Conclusions: THOR methylation may add information to differentiate normal from carcinogenic tissues and, as such, may be included in a biomarkers panel. Epigenetic alterations in PA-adjacent tissues with normal histology highlight the need for improved diagnostic markers.

端粒酶逆转录酶启动子在腮腺肿瘤和邻近腮腺组织中的甲基化状态:对恶性肿瘤复发和发展的影响的初步研究。
背景/目的:人类端粒酶逆转录酶(hTERT)的高甲基化肿瘤区(THOR)的甲基化可以预测肿瘤的侵袭性。这项初步研究旨在评估THOR甲基化作为涎腺多形性腺瘤(PA)复发/恶性转化的潜在生物标志物。方法:采用定量焦磷酸测序法对96例腮腺组织(包括良性和恶性腮腺组织)进行THOR甲基化评估,包括非肿瘤性腮腺组织、PA、复发性PA (rPA)、癌及其邻近组织。采用Sanger测序分析TERT启动子突变(TPMs)。结果:THOR甲基化在七组之间存在显著差异。恶性组织的THOR甲基化高于非肿瘤组织,而良性肿瘤与非肿瘤组织的THOR甲基化差异无统计学意义。与正常组织相比,rPA中THOR甲基化更接近癌组织,rPA与rPA邻近组织相似,癌邻近组织中THOR甲基化高于非肿瘤组织。一组pa邻近组织显示表观遗传改变,提示复发或恶性转化的风险增加(5-15%)。未检测到TPMs。结论:THOR甲基化可能增加了区分正常组织和致癌组织的信息,因此可能包括在生物标志物面板中。正常组织学的pa邻近组织的表观遗传改变强调了改进诊断标记的必要性。
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来源期刊
Current oncology
Current oncology ONCOLOGY-
CiteScore
3.30
自引率
7.70%
发文量
664
审稿时长
1 months
期刊介绍: Current Oncology is a peer-reviewed, Canadian-based and internationally respected journal. Current Oncology represents a multidisciplinary medium encompassing health care workers in the field of cancer therapy in Canada to report upon and to review progress in the management of this disease. We encourage submissions from all fields of cancer medicine, including radiation oncology, surgical oncology, medical oncology, pediatric oncology, pathology, and cancer rehabilitation and survivorship. Articles published in the journal typically contain information that is relevant directly to clinical oncology practice, and have clear potential for application to the current or future practice of cancer medicine.
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