Amplification of 3q26.2, 5q14.3, 8q24.3, 8q22.3, and 14q32.33 Are Possible Common Genetic Alterations in Oral Cancer Patients
Amplification of 3q26.2, 5q14.3, 8q24.3, 8q22.3, and 14q32.33 Are Possible Common Genetic Alterations in Oral Cancer Patients
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DOI：
10.3389/fonc.2020.00683
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发表时间：
2020-04-30
影响因子：
4.7
通讯作者：
van Heerden, Willie F. P.
中科院分区：
文献类型：
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作者：
Ambele, Melvin A.;van Zyl, Andre;van Heerden, Willie F. P.
头颈癌亚型临床生物标志物的缺乏限制了疾病进展的早期诊断和监测。本研究调查了五名口腔癌患者临床上相同的肿瘤、肿瘤邻近的发育不良上皮 (TADE) 和正常上皮 (NE) 的遗传改变，以确定口腔癌、TADE 和 NE 之间的差异和共性。 VELscope (R) Vx 装置用于识别临床肿瘤周围的 TADE 和 NE，以便使用 OncoScan (R) 检测分析遗传改变。检查的其中一个肿瘤样本是“M”类肿瘤，具有高置信度 BRAF:p.G469A:c.1406G>C 体细胞突变，这是口腔癌中首次报道的突变。另一个肿瘤显示出基因改变的镶嵌现象，表明存在多个克隆。总体而言，每位患者的肿瘤、TADE 和 NE 显示出独特的遗传图谱，表明肿瘤间克隆/遗传多样性。有趣的是，四个肿瘤显示 3q26.2、5q14.3、8q24.3、8q22.3、14q32.33 的增益和 9p21.3 的丢失/LOH，而所有 TADE 在 22q11.23 上都有 LOH。此外，一些基因改变从 NE 通过 TADE 进展到个别患者的肿瘤中。此外，没有发现所有进展为肿瘤的 NE 和/或 TADE 所共有的分子事件。这项初步研究证明了口腔肿瘤发生中存在遗传异质性，并表明肿瘤和 TADE 之间可能存在一些共同的遗传改变。然而，这一观察结果需要在更大的口腔癌患者群体中进行进一步研究和验证，以了解其在口腔肿瘤发生中的潜在作用。
The lack of clinical biomarkers for head and neck cancer subtypes limits early diagnosis and monitoring of disease progression. This study investigates genetic alterations in clinically identical tumor, tumor-adjacent dysplastic epithelium (TADE) and normal epithelium (NE) in five oral cancer patients to identify differences and commonalities between oral cancer, TADE and NE. A VELscope (R) Vx device was used to identify TADE and NE surrounding a clinical tumor for analysis of genetic alterations using the OncoScan (R) assay. One of the tumor samples examined was an "M" class tumor with a high confidence BRAF:p.G469A:c.1406G>C somatic mutation, which is the first to be reported in oral cancer. Another tumor showed mosaicism in genetic alterations, indicating the presence of multiple clones. Overall, each patient's tumor, TADE and NE showed a distinct genetic profile which indicates intertumoral clonal/genetic diversity. Interestingly, four tumors showed gain of 3q26.2, 5q14.3, 8q24.3, 8q22.3, 14q32.33 and loss/LOH in 9p21.3 while all TADE had LOH on 22q11.23. In addition, some genetic alterations progressed from NE through TADE into tumor in individual patients. Furthermore, no molecular event was identified that is common to all NE and/or TADE that progressed into tumor. This pilot study demonstrates the presence of genetic heterogeneity in oral tumorigenesis, and suggests that there might exist some common genetic alterations between tumors and TADE. However, this observation would need to be further investigated and validated in a larger cohort of oral cancer patients for its potential role in oral tumorigenesis.