Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
Cancer Biomark. 2022;33(1):29-41. doi: 10.3233/CBM-210275.
TP53 mutation is a driver mutation of oral carcinogenesis. This study investigated cancerous and cell-free DNA (cfDNA) in patients with oral squamous cell carcinoma (OSCC) to detect the target hotspot somatic mutation of TP53.
TP53 target hotspot mutations were determined in surgically resected primary tumor samples from 107 OSCC patients.
Cancerous and cfDNA samples were examined for mutations through droplet digital polymerase chain reaction (ddPCR) by using mutation-specific assays. The ddPCR results were evaluated alongside clinicopathological data.
In total, 23 cases had target TP53 mutations in varying degrees. We found that OSCC had relatively low cfDNA shedding, and mutations were at low allele frequencies. Of these 23 cases, 13 had target TP53 mutations in their corresponding cfDNA. Target somatic mutations in cancerous DNA and cfDNA are related to cervical lymph node metastasis. The cfDNA concentration is related to primary tumor size, lymph node metastasis, and OSCC stage.
Our results show that the detection of TP53 target somatic mutations in OSCC patients by using ddPCR is technically feasible. Low levels of cfDNA may produce different results between cancerous tissue and cfDNA analyses. Future research on cfDNA may quantify diagnostic biomarkers in the surveillance of OSCC patients.
TP53 突变是口腔癌发生的驱动突变。本研究通过检测口腔鳞状细胞癌（OSCC）患者的癌组织和游离 DNA（cfDNA），以检测 TP53 的靶热点体细胞突变。
检测 107 例 OSCC 患者手术切除的原发肿瘤样本中的 TP53 靶热点突变。
通过使用突变特异性检测，通过液滴数字聚合酶链反应（ddPCR）对癌组织和 cfDNA 样本中的突变进行检测。ddPCR 结果与临床病理数据进行评估。
共有 23 例存在不同程度的 TP53 靶基因突变。我们发现 OSCC 的 cfDNA 脱落率相对较低，且突变等位基因频率较低。在这 23 例中，有 13 例在对应的 cfDNA 中存在 TP53 靶基因突变。癌组织 DNA 和 cfDNA 中的靶体细胞突变与颈部淋巴结转移有关。cfDNA 浓度与原发肿瘤大小、淋巴结转移和 OSCC 分期有关。
我们的结果表明，ddPCR 检测 OSCC 患者的 TP53 靶基因突变在技术上是可行的。cfDNA 水平较低可能会导致癌组织和 cfDNA 分析之间产生不同的结果。未来对 cfDNA 的研究可能会在 OSCC 患者的监测中量化诊断生物标志物。
