Department of Dermatology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
J Oral Pathol Med. 2022 Apr;51(4):395-404. doi: 10.1111/jop.13284. Epub 2022 Mar 1.
Oral lichen planus confers a 1% risk of transformation to oral squamous cell carcinoma. While prior exome sequencing studies have identified multiple genetic mutations in oral squamous cell carcinoma, mutational analyses of lichen planus-derived OSCC are lacking. We sought to clarify genomic events associated with oral lichen planus transformation.
Using rigorous diagnostic criteria, we retrospectively identified patients with non-transforming oral lichen planus (i.e., known to be non-transforming with 5 years of clinical follow-up; n = 17), transforming oral lichen planus (tissue marginal to oral squamous cell carcinoma, n = 9), or oral squamous cell carcinoma arising in lichen planus (n = 17). Gene mutational profiles derived from whole-exome sequencing on fixed mucosal specimens were compared among the groups.
The four most frequently mutated genes in transforming oral lichen planus and oral squamous cell carcinoma (TP53, CELSR1, CASP8, and KMT2D) identified 12/17 (71%) of oral squamous cell carcinomas and 5/9 (56%) of transforming oral lichen planus but were absent in non-transforming oral lichen planus. We identified other known oral squamous cell carcinoma mutations (TRRAP, OBSCN, and LRP2) but also previously unreported mutations (TENM3 and ASH1L) in lichen planus-associated oral squamous cell carcinomas.
These findings suggest alterations in DNA damage response and apoptosis pathways underlie lichen planus-related oral squamous cell carcinoma transformation and are supported by mutational signatures indicative of DNA damage. This study characterized patterns of mutational events present in oral lichen planus associated with squamous cell carcinoma and in squamous cell carcinoma associated with oral lichen planus but not in non-transforming oral lichen planus.
口腔扁平苔藓发生口腔鳞状细胞癌的风险为 1%。虽然先前的外显子组测序研究已经在口腔鳞状细胞癌中发现了多种基因突变，但缺乏对扁平苔藓衍生的口腔鳞状细胞癌的突变分析。我们试图阐明与口腔扁平苔藓转化相关的基因组事件。
使用严格的诊断标准，我们回顾性地确定了非转化性口腔扁平苔藓患者（即已知在 5 年临床随访中不发生转化；n=17）、转化性口腔扁平苔藓（口腔鳞状细胞癌边缘组织，n=9）或口腔扁平苔藓衍生的口腔鳞状细胞癌（n=17）。比较了各组固定黏膜标本全外显子测序得出的基因突变谱。
在转化性口腔扁平苔藓和口腔鳞状细胞癌中最常突变的四个基因（TP53、CELSR1、CASP8 和 KMT2D）在 12/17（71%）口腔鳞状细胞癌和 5/9（56%）转化性口腔扁平苔藓中发现，但在非转化性口腔扁平苔藓中不存在。我们发现了其他已知的口腔鳞状细胞癌突变（TRRAP、OBSCN 和 LRP2），但也发现了扁平苔藓相关口腔鳞状细胞癌中以前未报道的突变（TENM3 和 ASH1L）。
这些发现表明，DNA 损伤反应和细胞凋亡途径的改变是扁平苔藓相关口腔鳞状细胞癌转化的基础，并得到了表明 DNA 损伤的突变特征的支持。本研究描述了与口腔扁平苔藓相关的口腔鳞状细胞癌和与口腔扁平苔藓相关的口腔鳞状细胞癌中存在的突变事件模式，但在非转化性口腔扁平苔藓中不存在。
