基于二代测序探索头颈部高级别转化腺样囊性癌分子遗传学特征  

Adenoid Cystic Carcinoma with High-grade Transformation in Head and Neck:An Exploration of Its Molecular Genetic Alterations Based on Next-generation Sequencing

作　　者：刘胜楠 顾挺 张莺 钱佳骏 薛俊青 王瑜 LIU Shengnan;GU Ting;ZHANG Ying;QIAN Jiajun;XUE Junqing;WANG Yu(Department of Oral Pathology,Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,College of Stomatology,Shanghai Jiao Tong University,National Center for Stomatology,National Clinical Research Center for Oral Diseases,Shanghai Key Laboratory of Stomatology,Shanghai Research Institute of Stomatology,Shanghai 200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院口腔病理科,上海交通大学医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海200011

出　　处：《口腔医学研究》2024年第2期161-165,共5页Journal of Oral Science Research

基　　金：国家自然科学基金青年项目(编号:82103405)。

摘　　要：目的:探索头颈部高级别转化腺样囊性癌(adenoid cystic carcinoma with high-grade transformation,ACC-HGT)的临床病理及分子遗传学特征。方法:收集自2020年1月~2022年12月上海第九人民医院口腔病理科诊断的5例高级别转化腺样囊性癌患者的临床病理资料,运用显微切割方法获得肿瘤的高级别转化成分以开展二代基因检测,接着利用免疫组织化学技术进一步验证基因突变对蛋白质生成水平的影响。结果:5例患者都是男性,平均年龄为48岁,追踪观察时间4~30个月,有3例仍然存活,2例已经去世,3例发现局部复发,2例出现血行转移至肺、脑。5例肿瘤中,NOTCH1突变在3例中检出,NOTCH1重排在1例中检出,p53突变在1例中检出,PIK3CA突变在2例中检出,PIK3R1突变在1例中检出,PPP2R2A突变在1例中检出,这些基因突变可引起其下游相关蛋白NICD、p53及PI3K信号通路相关蛋白pAKTSer473高表达。结论:ACC-HGT易复发和血行转移,其遗传改变主要发生在NOTCH、PI3K以及p53通路上。Objective:To identify the genetic alterations of ACC-HGT in the head and neck.Methods:Clinical and pathological information were gathered from five patients with ACC-HGT who were diagnosed in the Department of Oral Pathology at the Shanghai Ninth People's Hospital during the period from January 2020 to December 2022.The high-grade transformed components microdissected from the 5 cases were detected by next generation sequencing.The effect of gene mutations on protein expression was further verified by immunohistochemistry.Results:These patients were all male,whose average age was 48 years.During the period after surgery ranging from 4 to 30 months,the outcomes of 5 patients was tracked.Of these,3 survived while 2 deceased.Three patients experienced local recurrence,with 2 also developing distant metastases to lungs and brain.Of the 5 tumors,NOTCH1 mutations were detected in 3 cases and another one case harbored NOTCH1 rearrangement.p53 mutation was detected in 1 case.PIK3CA mutation was detected in 2 cases.PIK3R1 mutation was detected in 1 case.PPP2R2A mutation was detected in 1 case.These gene mutations could cause the overexpression of downstream related proteins NICD,p53 and pAKTSer473.Conclusion:Adenoid cystic carcinoma with high-grade transformation has a poor prognosis,and are enriched for alterations in the key NOTCH,PI3K and P53 signaling pathways.

关 键 词：腺样囊性癌 高级别转化 显微切割 NOTCH1 p53 PI3K 

分 类 号：R739.8[医药卫生—肿瘤]