Krishnan Reshma Poothakulath, Pandiar Deepak, Ramani Pratibha, Jayaraman Selvaraj
Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.
J Stomatol Oral Maxillofac Surg. 2024 Oct 17;126(4):102120. doi: 10.1016/j.jormas.2024.102120.
Next generation sequencing (NGS) is a massive, high-throughput sequencing technology used to analyze various mutations and genetic changes in cancer. Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and neck region. OSCC usually arises from oral potentially malignant disorders, like oral leukoplakia, oral submucous fibrosis and erythroplakia, and shows mutation of tumor suppressor genes, and several other critical genes involved in apoptotic pathways, cell migration, and cell growth.
To analyze the molecular profiles of oral epithelial dysplasia and different grades of oral squamous cell carcinoma using NGS in the Indian subpopulation.
21 patients (5 patients each of well differentiated, moderately differentiated, poorly differentiated squamous cell carcinoma, severe epithelial dysplasia, and 1 normal appearing mucosal tissue from apparently healthy individuals) were included in the study. Next generation sequencing was carried out using 50 hotspot gene panel. Protein-protein analysis was carried out using STRING Consortium 2023 and the methylation profile of the expressed genes was evaluated using the UALCAN portal.
Severe epithelial dysplasia showed TP53 (c.743G>A, p.R248Q) pathogenic mutations (SNV) in suboptimal QC parameters. Well differentiated squamous cell carcinoma showed TP53 (c.328delC, p.Arg110fs13), APC (c.4135G>T, p.Glu1379), and FBXW7 (c.832C>T, p.Arg278*) mutations. CTNNB1 (c.134C>T, p.Ser45PheS45F), TP53 (c.637C>T, Arg213TerR213*), NRAS (c.183A>C, p.Gln61HisQ61H) and PDGFRA (c.1672C>T, p.Arg558Cys) mutations were seen in moderately differentiated squamous cell carcinoma. No pathogenic mutations were evident in poorly differentiated squamous cell carcinoma. STRING analysis showed that all the expressed proteins in each group were interrelated to each other. No significant difference was evident in the methylation profile of all the expressed genes when compared to the normal controls.
The results obtained in this study explain the diverse genetic mutations in various grades of oral squamous cell carcinoma. Identification of these mutations would help in providing better treatment, designing a proper treatment plan for the patients with OSCC and support minimal intervention medicine.
下一代测序（NGS）是一种大规模、高通量测序技术，用于分析癌症中的各种突变和基因变化。口腔鳞状细胞癌（OSCC）是头颈部最常见的恶性肿瘤。OSCC通常起源于口腔潜在恶性疾病，如口腔白斑、口腔黏膜下纤维化和红斑，并表现出肿瘤抑制基因以及参与凋亡途径、细胞迁移和细胞生长的其他几个关键基因的突变。
利用NGS分析印度亚人群中口腔上皮发育异常和不同分级的口腔鳞状细胞癌的分子特征。
本研究纳入21例患者（高分化、中分化、低分化鳞状细胞癌各5例，重度上皮发育异常5例，1例来自表面健康个体的外观正常黏膜组织）。使用50个热点基因panel进行下一代测序。使用STRING Consortium 2023进行蛋白质-蛋白质分析，并使用UALCAN门户评估表达基因的甲基化谱。
在次优质量控制参数下，重度上皮发育异常显示TP53（c.743G>A，p.R248Q）致病性突变（单核苷酸变异）。高分化鳞状细胞癌显示TP53（c.328delC，p.Arg110fs13）、APC（c.4135G>T，p.Glu1379）和FBXW7（c.832C>T，p.Arg278*）突变。中分化鳞状细胞癌可见CTNNB1（c.134C>T，p.Ser45PheS45F）、TP53（c.637C>T，Arg213TerR213*）、NRAS（c.183A>C，p.Gln61HisQ61H）和PDGFRA（c.1672C>T，p.Arg558Cys）突变。低分化鳞状细胞癌未见致病性突变。STRING分析表明，每组中所有表达的蛋白质相互关联。与正常对照相比，所有表达基因的甲基化谱无明显差异。
本研究获得的结果解释了不同分级口腔鳞状细胞癌中的多种基因突变。识别这些突变将有助于提供更好的治疗，为OSCC患者设计合适的治疗方案，并支持最小干预医学。
