The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

By Nicolas Stransky, A. Egloff, Aaron D. Tward, Aleksandar D. Kostic, Kristian Cibulskis, A. Sivachenko, G. Kryukov, M. Lawrence, C. Sougnez, A. McKenna and 29 more. Science, 2011

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The mutational profile of head and neck cancer is complex and may pose challenges to the development of targeted therapies. 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9e9740965406c913e76602885f7d0a9017f6bc57

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Citations in the corpus

A Landscape of Driver Mutations in Melanoma (2012, methodology): “For example, RAC1 P29S mutation has been reported in a head and neck tumor (Stransky et al., 2011) and in a breast tumor (Forbes et al., 2011); furthermore, homologous P29 mutations in other Rho family members were observed in melanoma (Figure 3).”
Next-generation sequencing data interpretation: enhancing reproducibility and accessibility (2012, background): “The other study published in the same issue carried out resequencing in an independent set of 92 patients and identified seven NOTCH1 missense mutations in 11% of studied tumours 17 .”
Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing (2012, methodology): “DLBCL sample and matched normal sample from peripheral blood (hg19) and performs various analyses (15, 16).”
Absolute quantification of somatic DNA alterations in human cancer (2012, background): “…and ploidy estimates with expression subtypes and to develop statistical power calculations and use them to select well-powered samples for whole-genome sequencing in several published 22, 23, 24 , and numerous ongoing projects, including breast, prostate, and skin cancer genome characterization.”