日本口腔鳞状细胞癌患者的突变景观：基因组全景分析
Mutational landscape of Japanese patients with oral squamous cell carcinoma from comprehensive genomic profiling tests
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影响因子:3.9
分区:医学2区 / 牙科与口腔外科2区 肿瘤学3区
发表日期:2024 Dec
作者:
Norihisa Ichimura, Yusuke Urata, Takeru Kobayashi, Ryo Ebata, Hiroya Matsumoto, Hideharu Hibi
DOI:
10.1016/j.oraloncology.2024.107079
摘要
口腔鳞状细胞癌（OSCC）是头颈部鳞状细胞癌（HNSCC）中最常见的亚型。由于缺乏明确的治疗靶点，OSCC的治疗选择有限。本研究旨在分析日本OSCC患者的基因组特征，并与HNSCC患者进行比较，以识别潜在的治疗靶点。我们从癌症基因组与治疗数据库中提取了2019年6月至2024年4月期间接受全面基因组分析的OSCC患者（n=242）和其他HNSCC患者（n=402）的临床及基因组信息。OSCC中最常见的基因突变为TP53（85.5%），其次是TERT（62.4%）、CDKN2A（41.3%）、FGF19（24.9%）和CCND1（23.6%）。FGF19与CCND1共扩增，CDKN2A与CDKN2B共同缺失。在所有HNSCC亚型中，OSCC中TERT、HRAS和CASP8的突变频率最高。与其他年龄组相比，青少年和年轻成人中的EGFR突变频率显著更高。涉及基因组稳定性和RTK-RAS通路的基因在OSCC中频繁突变。本研究分析了日本OSCC患者的基因组特征及其与其他HNSCC亚型的差异，为个性化治疗的发展提供了新的见解。
Abstract
Oral squamous cell carcinoma (OSCC) is the most common subtype of head and neck squamous cell carcinoma (HNSCC). Treatment options for OSCC are currently limited owing to the lack of identified therapeutic targets. In this study, we aimed to analyze the genomic profiles of Japanese patients with OSCC and compare them to those of patients with HNSCC to identify potential therapeutic targets.We extracted the clinical and genomic information of patients with OSCC (n = 242) and those with other HNSCC (n = 402) who underwent comprehensive genomic profiling tests under the National Health Insurance between June 2019 and April 2024 from the Center for Cancer Genomics and Therapeutics database.The most frequent genomic alterations identified in OSCC were TP53 (85.5 %), followed by TERT (62.4 %), CDKN2A (41.3 %), FGF19 (24.9 %), and CCND1 (23.6 %). FGF19 and CCND1 were co-amplified, and CDKN2A and CDKN2B were co-deleted. The frequencies of TERT, HRAS, and CASP8 alterations were the highest in OSCC among all HNSCC subtypes. The frequency of EGFR alterations was substantially higher in adolescent and young adults than older patients with OSCC. Genes associated with genomic integrity and the RTK-RAS pathway were frequently altered in OSCC.This study analyzed the genomic profiles of patients with OSCC in Japan and the genetic differences between OSCC and other HNSCC subtypes. This analysis offers insights into the development of personalized therapeutics for OSCC.