Scientific Publications

The mutational landscape of head and neck squamous cell carcinoma.

Publication TypeJournal Article
AuthorsStransky, N., Egloff AM, Tward AD, Kostic AD, Cibulskis K., Sivachenko A., Kryukov GV, Lawrence MS, Sougnez C., McKenna A., Shefler E., Ramos AH, Stojanov P., Carter SL, Voet D., Cortés ML, Auclair D., Berger MF, Saksena G., Guiducci C., Onofrio RC, Parkin M., Romkes M., Weissfeld JL, Seethala RR, Wang L., Rangel-Escareño C., Fernandez-Lopez JC, Hidalgo-Miranda A., Melendez-Zajgla J., Winckler W., Ardlie K., Gabriel SB, Meyerson M., Lander E. S., Getz G., Golub T. R., Garraway LA, and Grandis JR
AbstractHead 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 Publication2011
JournalScience (New York, N.Y.)
Volume333
Issue6046
Pages1157-60
Date Published (YYYY/MM/DD)2011/08/26
ISSN Number0036-8075
DOI10.1126/science.1208130
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/21798893?dopt=Abstract