The mutational landscape of head and neck squamous cell carcinoma.
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.
|Year of Publication||
2011 Aug 26
|PubMed Central ID||
UL1 TR000005 / TR / NCATS NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
R01 CA077308 / CA / NCI NIH HHS / United States
R01 CA098372 / CA / NCI NIH HHS / United States
P50 CA097190 / CA / NCI NIH HHS / United States
Howard Hughes Medical Institute / United States