title: 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.
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Bhaduri
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Mah
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Whitney L
authors.initials: WL
authors.lastname: Johnson
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ungewickell
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Aros
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Christie B
authors.initials: CB
authors.lastname: Nguyen
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Eon J
authors.initials: EJ
authors.lastname: Rios
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Zurab
authors.initials: Z
authors.lastname: Siprashvili
authors.affiliation: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Straight
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Jinah
authors.initials: J
authors.lastname: Kim
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Sumaira Z
authors.initials: SZ
authors.lastname: Aasi
authors.affiliation: 1] Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA. [2] Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Khavari
mesh_terms: D000782:Aneuploidy; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D018386:Kinetochores / Q000378:metabolism*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D017354:Point Mutation; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D018797:Cell Cycle Proteins; C555984:KNSTRN protein, human; D008869:Microtubule-Associated Proteins