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Updated: Mar 23, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Somatic Mutations and Genetic Variants of NOTCH1 in Head and Neck Squamous Cell Carcinoma Occurrence and Development
Yu-Fan Liu1,2, Shang-Lun Chiang3,4, Chien-Yu Lin5,6
1Department of Biomedical Sciences, College of Medicine Sciences and Technology, Chung Shan Medical University, Taichung, Taiwan.
Abstract:
A number of genetic variants have been associated with cancer occurrence, however it may be the acquired somatic mutations (SMs) that drive cancer development. This study investigates the potential SMs and related genetic variants associated with the occurrence and development of head and neck squamous cell carcinoma (HNSCC). We identified several SMs in NOTCH1 from whole-exome sequencing and validated them in a 13-year cohort of 128 HNSCC patients using a high-resolution melting analysis and resequencing. Patients who have NOTCH1 SMs show higher 5-year relapse-free recurrence (P = 0.0013) and lower survival proportion (P = 0.0447) when the risk-associated SMs were analysed by Cox proportional hazard models. Interestingly, the NOTCH1 gene rs139994842 that shares linkage with SMs is associated with HNSCC risk (OR = 3.46), increasing when SMs in NOTCH1 are involved (OR = 7.74), and furthermore when there are SMs in conjunction to betel quid chewing (OR = 32.11), which is a related independent environmental risk factor after adjusting for substances use (alcohol, betel quid, cigarettes) and age. The findings indicate that betel quid chewing is highly associated with NOTCH1 SMs (especially with changes in EGF-like domains), and that rs139994842 may potentially serve as an early predictive and prognostic biomarker for the occurrence and development of HNSCC.
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