Department of Genetics, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, FCT 10.6008, 77030, TX, Houston, USA.
The Francis Crick Institute, London, UK.
Sci Rep. 2024 Sep 30;14(1):22591. doi: 10.1038/s41598-024-72946-3.
Oral potentially malignant disorders (OPMDs) with genomic alterations have a heightened risk of evolving into oral squamous cell carcinoma (OSCC). Currently, genomic data are typically obtained through invasive tissue biopsy. However, brush biopsy is a non-invasive method that has been utilized for identifying dysplastic cells in OPMD but its effectiveness in reflecting the genomic landscape of OPMDs remains uncertain. This pilot study investigates the potential of brush biopsy samples in accurately reconstructing the genomic profile and tumor evolution in a patient with both OPMD and OSCC. We analyzed single nucleotide variants (SNVs), copy number aberrations (CNAs), and subclonal architectures in paired tissue and brush biopsy samples. The results showed that brush biopsy effectively captured 90% of SNVs and had similar CNA profiles as those seen in its paired tissue biopsies in all lesions. It was specific, as normal buccal mucosa did not share these genomic alterations. Interestingly, brush biopsy revealed shared SNVs and CNAs between the distinct OPMD and OSCC lesions from the same patient, indicating a common ancestral origin. Subclonal reconstruction confirmed this shared ancestry, followed by divergent evolution of the lesions. These findings highlight the potential of brush biopsies in accurately representing the genomic profile of OPL and OSCC, proving insight into reconstructing tumor evolution.
口腔潜在恶性疾病（OPMD）伴基因组改变有发展为口腔鳞状细胞癌（OSCC）的高风险。目前，基因组数据通常通过有创的组织活检获得。然而，刷检是一种非侵入性的方法，已用于识别 OPMD 中的异型细胞，但它在反映 OPMD 基因组景观方面的有效性仍不确定。本研究旨在探讨刷检样本在准确重建 OPMD 伴 OSCC 患者的基因组特征和肿瘤演变方面的潜力。我们分析了配对组织和刷检样本中的单核苷酸变异（SNVs）、拷贝数异常（CNAs）和亚克隆结构。结果表明，刷检有效地捕获了 90%的 SNVs，并且在所有病变中与配对组织活检的 CNA 图谱相似。它具有特异性，因为正常颊黏膜没有这些基因组改变。有趣的是，刷检揭示了来自同一患者的不同 OPMD 和 OSCC 病变之间存在共同的 SNVs 和 CNAs，表明存在共同的起源。亚克隆重建证实了这种共同的起源，随后病变发生了分歧性演变。这些发现突出了刷检在准确代表 OPL 和 OSCC 基因组特征方面的潜力，为重建肿瘤演变提供了新的见解。
