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Recurrent point mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma

2014; Nature Portfolio; Volume: 46; Issue: 10 Linguagem: Inglês

10.1038/ng.3091

1546-1718

Carolyn Lee, Aparna Bhaduri, Angela Mah, Whitney L. Johnson, Alexander Ungewickell, Cody J. Aros, Christie B. Nguyen, Eon J. Rios, Zurab Siprashvili, Aaron F. Straight, Jinah Kim, Sumaira Z. Aasi, Paul A. Khavari,

Cancer Genomics and Diagnostics

Paul Khavari and colleagues identify recurrent mutations concentrated at an ultraviolet signature hotspot in the KNSTRN gene in 19% of cutaneous squamous cell carcinomas. KNSTRN encodes a kinetochore protein. Here we report the discovery of recurrent mutations concentrated at an ultraviolet signature hotspot in KNSTRN, which encodes a kinetochore protein, in 19% of cutaneous squamous cell carcinomas (SCCs). Cancer-associated KNSTRN mutations, most notably those encoding p.Ser24Phe, disrupt chromatid cohesion in normal cells, occur in SCC precursors, correlate with increased aneuploidy in primary tumors and enhance tumorigenesis in vivo. These findings suggest a role for KNSTRN mutagenesis in SCC development.