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

Nat Genet. 2014 Oct;46(10):1060-2. doi: 10.1038/ng.3091. Epub 2014 Sep 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aneuploidy
  • Animals
  • Carcinogenesis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Cells, Cultured
  • Female
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Keratinocytes / transplantation
  • Kinetochores / metabolism*
  • Mice, Inbred NOD
  • Mice, SCID
  • Microtubule-Associated Proteins / genetics*
  • Point Mutation*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Transfection
  • Transplantation, Heterologous

Substances

  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • SKAP protein, human

Associated data

  • dbGaP/PHS000785.V1.P1