Jensen Jakob Myllerup, Sjöstedt Sannia Mia Svenningsen, Carmona Javiera Laing, Ahlborn Lise Barlebo, Vieira Filipe Garrett, Nielsen Finn Cilius, Kiss Katalin, Grønhøj Christian, von Buchwald Christian
Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Front Oncol. 2024 Sep 11;14:1450361. doi: 10.3389/fonc.2024.1450361. eCollection 2024.
The aim of this study was to investigate the genomic changes that occur in the development from dysplasia, cancer and to regional metastases in patients with oral cavity squamous cell carcinoma (OSCC).
We included OSCC patients with lymph node metastases at diagnosis, treated with primary surgery at Rigshospitalet, University of Copenhagen in the period 2007-2014. The resected tumor specimens were evaluated by a pathologist, who marked areas of morphologically normal tissue and dysplasia surrounding the cancer, two areas from the cancer tissue, and one area within the lymph node metastases. From these areas a punch biopsy was taken, and DNA from each sample was extracted and sequenced using Illumina's TSO500 HT cancer panel.
From 51 OSCC patients, 255 samples were included, comprising a wide variety of genomic alterations. Substantial intratumor heterogeneity was found. The most commonly mutated gene was , mutated in 65% of all samples. Only two patients had no mutation in any samples. We found that morphologically normal appearing mucosa as well as surrounding dysplasia also contained malignant mutations, supporting the theory of field cancerization. There was a significant lower average tumor mutational burden (TMB) in the lymph node metastases compared to the primary tumors, supporting the theory of clonal selection.
Substantial inter- and intratumor genomic heterogeneity was found. Mutation of was the most common and was present in all but two patients. Our data strongly supports the theory of clonal selection and the theory of field cancerization.
本研究的目的是调查口腔鳞状细胞癌（OSCC）患者从发育异常、癌症发展到区域转移过程中发生的基因组变化。
我们纳入了2007年至2014年期间在哥本哈根大学 Rigshospitalet 接受初次手术治疗、诊断时伴有淋巴结转移的OSCC患者。切除的肿瘤标本由病理学家进行评估，病理学家标记形态学上正常的组织区域以及癌症周围的发育异常区域、癌症组织的两个区域和淋巴结转移灶内的一个区域。从这些区域进行打孔活检，提取每个样本的DNA，并使用Illumina的TSO500 HT癌症检测板进行测序。
纳入了51例OSCC患者的255个样本，包含各种各样的基因组改变。发现了显著的肿瘤内异质性。最常发生突变的基因是 ，在所有样本中的突变率为65%。只有两名患者的任何样本中均未发生 突变。我们发现形态学上看似正常的黏膜以及周围的发育异常区域也含有恶性突变，支持了场癌化理论。与原发性肿瘤相比，淋巴结转移灶中的平均肿瘤突变负荷（TMB）显著降低，支持了克隆选择理论。
发现了显著的肿瘤间和肿瘤内基因组异质性。 突变是最常见的，除两名患者外所有患者均存在该突变。我们的数据有力地支持了克隆选择理论和场癌化理论。
