DNA methylation analysis from oral brushing reveals a field cancerization effect in proliferative verrucous leukoplakia.

IF 4.4 Q1 PATHOLOGY
Andrea Gabusi, Davide Bartolomeo Gissi, Giulia Querzoli, Asia Sangiovanni, Roberto Rossi, Elisabetta Lucchi, Achille Tarsitano, Lucio Montebugnoli, Maria Pia Foschini, Luca Morandi
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引用次数: 0

Abstract

Objectives: The aim of the present study was to analyze the methylation status in patients who presented with an Oral Squamous Cell Carcinoma (OSCC) concomitantly with multifocal Proliferative Verrucous Leukoplakia (PVL)(PVL-OSCC).

Methods: Nine patients with OSCC and concomitant PVL lesions were selected. Two brushing samples were collected simultaneously from OSCC and PVL lesions in contralateral mucosa from each patient. 15 genes (272 CpGs) were used to compare methylation profiles of PVL-OSCC and paired OSCC. CpGs with a methylation level superimposable between PVL-OSCC and contralateral OSCC were selected for a comparative analysis between PVL-OSCC, 8 PVL patients with no history of OSCC (PVL) and 23 healthy donors. Samples were also tested using an algorithm that was recently validated for epigenetic alterations in OSCC.

Results: 220/272 CpGs islands (80%) showed a superimposable methylation level in OSCC and in PVL-OSCC. 10 genes (88 CpGs) and in particular PARP15 and ITGA4 (100% of the studied CpGs) were able to stratify PVL-OSCC from PVL and healthy donors. 3/4 (75%) PVL-OSCC patients with a "positive" algorithm score developed second neoplastic events compared to only 1/5 (20%) patients with a "negative" score.

Conclusions: The present study provides evidence that PVL shares an aberrant methylation profile with contralateral OSCC. In agreement with the theory of field cancerization, our data point towards the potential role of epigenetics in patients at risk of developing multiple neoplastic events.

口腔刷牙的DNA甲基化分析揭示了增生性疣状白斑的场癌效应。
目的:本研究的目的是分析口腔鳞状细胞癌(OSCC)合并多灶增殖性疣状白斑(PVL-OSCC)患者的甲基化状态。方法:选择9例OSCC合并PVL病变的患者。同时从患者对侧粘膜OSCC和PVL病变处采集两份刷检标本。使用15个基因(272个CpGs)比较PVL-OSCC和配对的OSCC的甲基化谱。选择PVL-OSCC和对侧OSCC之间具有甲基化水平重叠的CpGs,对PVL-OSCC、8例无OSCC病史的PVL患者(PVL)和23例健康供者进行比较分析。样品也使用一种算法进行测试,该算法最近被验证用于OSCC的表观遗传改变。结果:220/272个CpGs岛(80%)在OSCC和PVL-OSCC中显示重叠的甲基化水平。10个基因(88个CpGs),特别是PARP15和ITGA4(100%的研究CpGs)能够将PVL- oscc从PVL和健康供体中分层。算法评分为“阳性”的PVL-OSCC患者中有3/4(75%)发生第二次肿瘤事件,而评分为“阴性”的患者中只有1/5(20%)发生第二次肿瘤事件。结论:本研究提供了PVL与对侧OSCC共享异常甲基化谱的证据。与野癌理论一致,我们的数据指向了表观遗传学在有发生多种肿瘤事件风险的患者中的潜在作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
PATHOLOGICA
PATHOLOGICA PATHOLOGY-
CiteScore
5.90
自引率
5.70%
发文量
108
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