Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Genome Analysis Center, Yamanashi Prefectural Central Hospital, Yamanashi, Japan.
Cancer Med. 2021 Jun;10(11):3545-3555. doi: 10.1002/cam4.3905. Epub 2021 May 2.
Somatic mutations including the background mucosa in patients with Lugol-voiding lesions (LVLs) are still not well known. The aim of this study was to evaluate the somatic mutations of the background mucosa in patients with LVLs (Squamous cell carcinoma (SCC), intraepithelial neoplasia (IN), and hyperplasia). Twenty-five patients with LVLs (9 with SCC, 6 with IN, and 10 with hyperplasia) were included. A targeted sequence was performed for LVLs and background mucosa using an esophageal cancer panel. Each mutation was checked whether it was oncogenic or not concerning OncoKB. In LVLs, TP53 was the most dominant mutation (80%). Furthermore, 72% of TP53 mutations was putative drivers. In background mucosa, NOTCH1 was the most dominant mutation (88%) and TP53 was the second most dominant mutation (48%). Furthermore, 73% of TP53 mutations and 8% of NOTCH1 mutations were putative drivers. Putative driver mutations of TP53 had significantly higher allele frequency (AF) in SCC than in IN and hyperplasia. Conversely, putative driver mutations of NOTCH1 did not have a significant accumulation of AF in the progression of carcinogenesis. Furthermore, in SCC, AF of TP53 mutations was significantly higher in LVLs than in background mucosa, but not in IN and hyperplasia. Regarding NOTCH1, a significant difference was not observed between LVLs and background mucosa in each group. The background mucosa in patients with LVLs already had putative driver mutations such as TP53 and NOTCH1. Of these two genes, TP53 mutation could be the main target gene of carcinogenesis in esophageal SCC. Clinical Trials registry: UMIN000034247.
患者卢戈氏（Lugol）有浓染区病变（LVLs）的体突变，包括背景黏膜，仍知之甚少。本研究旨在评估 LVLs 患者（鳞状细胞癌（SCC）、上皮内瘤变（IN）和增生）背景黏膜的体细胞突变。纳入 25 例 LVLs 患者（9 例 SCC、6 例 IN 和 10 例增生）。采用食管癌panel 对 LVLs 和背景黏膜进行靶向测序。根据 OncoKB，对每个突变是否为致癌突变进行检查。在 LVLs 中，TP53 是最主要的突变（80%）。此外，72%的 TP53 突变是假定的驱动突变。在背景黏膜中，NOTCH1 是最主要的突变（88%），TP53 是第二主要的突变（48%）。此外，73%的 TP53 突变和 8%的 NOTCH1 突变是假定的驱动突变。TP53 的假定驱动突变在 SCC 中的等位基因频率（AF）显著高于 IN 和增生。相反，NOTCH1 的假定驱动突变在癌发生进展中并没有显著积累 AF。此外，在 SCC 中，LVLs 中 TP53 突变的 AF 明显高于背景黏膜，但在 IN 和增生中则不然。关于 NOTCH1，在每组中，LVLs 与背景黏膜之间均未观察到显著差异。LVLs 患者的背景黏膜已经存在 TP53 和 NOTCH1 等假定的驱动突变。在这两个基因中，TP53 突变可能是食管 SCC 发生的主要靶基因。临床试验注册号：UMIN000034247。
