The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

TLDR

Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. The study aims to uncover the mutational spectrum of HNSCC by analyzing whole‑exome sequencing data from 74 tumor‑normal pairs. Whole‑exome sequencing of 74 matched tumor‑normal pairs was performed to identify somatic mutations. The sequencing revealed a tobacco‑associated mutational profile, HPV presence in infected tumors, known driver mutations (TP53, CDKN2A, PTEN, PIK3CA, HRAS), numerous novel genes, and that at least 30 % of cases harbored mutations in squamous‑differentiation regulators such as NOTCH1, IRF6, and TP63, underscoring the power of large‑scale sequencing to uncover key carcinogenic mechanisms.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.