Decoding the genomic landscape of adenoid cystic carcinoma: a retrospective cohort study of MYB family alterations, NOTCH pathway activation, and clinical outcomes

作者：Jun Wu, Zhao Xi, Yi-Xuan Liu, Tianyu Ma, Yang Zhao, Guoliang Yang, Xiaohong Chen · 发表于：Translational Cancer Research · 年份：2025 · DOI：10.21037/tcr-2025-890 · 研究领域：Salivary Gland Tumors Diagnosis and Treatment、Hedgehog Signaling Pathway Studies、Thyroid Cancer Diagnosis and Treatment

Background: Adenoid cystic carcinoma (ACC) of the head and neck is a rare malignancy with suboptimal outcomes despite multimodal therapy. High recurrence rates and chemoradiation resistance underscore the unmet need for molecularly guided strategies. The aim of this study was to explore the influence of clinical characteristics and molecular stratification on prognosis. Methods: This investigation employs integrated molecular profiling of 182 ACC specimens to delineate clinically actionable genetic alterations. Inclusion required: (I) histologically confirmed ACC; (II) surgery and adjuvant radiotherapy; and (III) ≥36-month follow-up with quarterly imaging. MYB fusions and NOTCH activation were assessed via next-generation sequencing (NGS). Multivariate Cox models adjusted for tumor stage (T stage), histology, and metastasis evaluated recurrence and survival. Results: Patients (median age: 45.24 years; T4: 37.4%) exhibited: MYB alterations (59.90%), isolated NOTCH activation (6.00%), and co-alterations (7.10%). After covariate adjustment, MYB/NOTCH co-alterations predicted the poorest outcomes: 76.9% recurrence rate [adjusted hazard ratio (HR) =5.945; 95% confidence interval (CI): 2.318-15.162; P<0.001]and 69.2% mortality (HR =7.856; 95% CI: 3.024-20.406; P<0.001), significantly surpassing isolated MYB (33.9% recurrence, P=0.04) or NOTCH (63.6% recurrence, P=0.02) subgroups. The all-cause mortality rate was 30.22% (55/182). The median survival time for the co-alterations group...