DNA rare copy number alterations in Reinke’s Edema

Abstract Introduction: Reinke’s Edema (RE) is a laryngeal lesion related to excessive tobacco smoking, voice overuse, and laryngopharyngeal reflux. Although the risk of malignancy has been considered low in literature, RE is classified among precancerous lesions. Objectives: We investigated DNA Copy Number Alterations (CNAs) in specimens of RE and its potential association with malignant progression. Methods: We used array-based comparative genomic hybridization (aCGH, Agilent 4 × 180 K platform) to study eight RE cases. All patients were heavy tobacco users for at least 30 years, and none of them progressed to cancer in the follow-up (>8 years). Two RE presented mild dysplasia, one moderate dysplasia, and no histological alterations were found in the remaining five cases. CNAs were compared with the Database of Genomic Variants (DGV) and genes mapped on altered regions had their functions annotated. Results: Six of eight patients showed different rare copy number alterations on chromosomes 2q37.3, 4q13.1, 4q13.3, 7q11.22, 10p14, and 13q34. A gain of the whole chromosome 8 were detected in one case. Of interest, four of eight RE cases showed copy number imbalances involving genes previously described in several tumor types (RASA3, COL6A3, LINC00707, LINP1, SMR3A, and SMR3B). Conclusion: The genomic imbalances herein found in RE have the potential to contribute to the phenotype but with limited or no risk of cancer. A long-term follow-up in a large series of patients could clarify the mechanisms involved in the malignant progression of RE. Level of evidence: 4.

摘要 引言：雷克水肿（Reinke’s Edema, RE）是一种与过度吸烟、用声过度及喉咽反流相关的喉部病变。尽管现有文献认为其恶性转化风险较低，但雷克水肿仍被归类为癌前病变。
研究目的：本研究旨在分析雷克水肿（RE）标本中的DNA拷贝数变异（Copy Number Alterations, CNAs），并探讨其与恶性进展的潜在关联。
研究方法：我们采用基于芯片的比较基因组杂交技术（array-based comparative genomic hybridization, aCGH，安捷伦4×180 K芯片平台）对8例RE患者标本开展检测。所有受试者均为重度吸烟者，吸烟史至少30年，且随访时长＞8年期间均未进展为恶性肿瘤。其中2例存在轻度异型增生，1例为中度异型增生，剩余5例未检出组织学改变。将检测到的拷贝数变异与基因组变异数据库（Database of Genomic Variants, DGV）进行比对，并对变异区域内的基因进行功能注释。
研究结果：8例患者中，6例在染色体2q37.3、4q13.1、4q13.3、7q11.22、10p14及13q34区域存在罕见拷贝数变异。1例患者检出整条8号染色体拷贝数增加。值得注意的是，8例中有4例存在涉及多种肿瘤类型中已报道基因的拷贝数失衡，包括RASA3、COL6A3、LINC00707、LINP1、SMR3A及SMR3B。
研究结论：本研究在RE中检测到的基因组失衡可能参与病变表型的形成，但癌症发生风险有限或无风险。后续可通过大样本患者的长期随访，阐明雷克水肿恶性进展的潜在分子机制。
证据等级：4级。