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

ABSTRACT: 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.

SUBMITTER: Lee CS

PROVIDER: S-EPMC4324615 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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

Lee Carolyn S CS Bhaduri Aparna A Mah Angela A Johnson Whitney L WL Ungewickell Alexander A Aros Cody J CJ Nguyen Christie B CB Rios Eon J EJ Siprashvili Zurab Z Straight Aaron A Kim Jinah J Aasi Sumaira Z SZ Khavari Paul A PA

Nature genetics 20140907 10

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 deve ...[more]

PMID: 25194279

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