Koo Kendrick, Mouradov Dmitri, Angel Christopher M, Iseli Tim A, Wiesenfeld David, McCullough Michael J, Burgess Antony W, Sieber Oliver M
Personalised Oncology Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, VIC 3052, Australia.
Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
Cancers (Basel). 2021 Mar 1;13(5):1029. doi: 10.3390/cancers13051029.
Molecular alterations in 176 patients with oral squamous cell carcinomas (OSCC) were evaluated to delineate differences in non-smoking non-drinking (NSND) patients. Somatic mutations and DNA copy number variations (CNVs) in a 68-gene panel and human papilloma virus (HPV) status were interrogated using targeted next-generation sequencing. In the entire cohort, (60%) and (24%) were most frequently mutated, and the most common CNVs were amplifications (9%) and deletions of (5%) and (4%). Significant associations were found for mutation and nodal disease, lymphovascular invasion and extracapsular spread, mutation or deletion with advanced tumour stage, and amplification with perineural invasion and extracapsular spread. mutation, deletion, and amplification were associated with worse survival in univariate analyses ( < 0.05 for all comparisons). There were 59 NSND patients who tended to be female and older than patients who smoke and/or drink, and showed enrichment of mutations, amplifications, and deletions ( < 0.05 for all comparisons), with a younger subset showing higher mutation burden. HPV was detected in three OSCC patients and not associated with smoking and drinking habits. NSND OSCC exhibits distinct genomic profiles and further exploration to elucidate the molecular aetiology in these patients is warranted.
对176例口腔鳞状细胞癌（OSCC）患者的分子改变进行评估，以明确非吸烟非饮酒（NSND）患者的差异。使用靶向二代测序技术检测了一个68基因panel中的体细胞突变和DNA拷贝数变异（CNV）以及人乳头瘤病毒（HPV）状态。在整个队列中， （60%）和 （24%）是最常发生突变的基因，最常见的CNV是 扩增（9%）以及 的缺失（5%）和 （4%）。发现 突变与淋巴结疾病、淋巴管浸润和包膜外扩散显著相关， 突变或缺失与肿瘤晚期相关， 扩增与神经周围浸润和包膜外扩散相关。在单因素分析中， 突变、 缺失和 扩增与较差的生存率相关（所有比较中P<0.05）。有59例NSND患者，她们往往比吸烟和/或饮酒的患者年龄更大且为女性，并且显示 突变、 扩增和 缺失富集（所有比较中P<0.05），其中较年轻的亚组显示出更高的突变负担。在3例OSCC患者中检测到HPV，且其与吸烟和饮酒习惯无关。NSND OSCC表现出独特的基因组特征，因此有必要进一步探索以阐明这些患者的分子病因。
