Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002–2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence ofNFIB-MYBrearrangement at the 6q23.3 locus; 35% had mutations inNOTCHpathway genes; 7% of patients had aNOTCH1mutation, 14.3%NOTCH2mutation, and 14.3%NOTCH3mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets.
头颈部来源的腺样囊性癌（ACC）具有进展缓慢但持续恶化并发生全身转移的特点，导致长期生存率较低。该肿瘤对常规化疗不敏感。明确其分子驱动因素可为个体化治疗提供理论依据。本研究对爱尔兰地区一组患者的临床特征及详细分子基因组学特征进行分析，探讨原发部位、分子特征与预后的相关性。我们采用荧光原位杂交、DNA测序及生物信息学分析技术，对爱尔兰某单一医疗中心二十年间（2002-2022年）所有确诊ACC患者的临床及基因组学特征进行系统性研究。共纳入14例患者进行分析，其中11例为原发性唾液腺ACC，3例为原发性泪腺ACC。76.9%的肿瘤检测显示6q23.3位点存在NFIB-MYB基因重排；35%携带NOTCH通路基因突变（NOTCH1突变7%，NOTCH2突变14.3%，NOTCH3突变14.3%）。表观遗传修饰的存在与患者总生存期显著缩短密切相关。本研究揭示了驱动ACC发病的关键基因突变及信号通路，为潜在分子靶点与治疗策略提供了新方向。
Molecular Analysis of Salivary and Lacrimal Adenoid Cystic Carcinoma
肿瘤(癌症)患者之家