title: Frequency and distribution of Notch mutations in tumor cell lines.
abstract: BACKGROUND
  Deregulated Notch signaling is linked to a variety of tumors and it is therefore important to learn more about the frequency and distribution of Notch mutations in a tumor context.
  
  
  METHODS
  In this report, we use data from the recently developed Cancer Cell Line Encyclopedia to assess the frequency and distribution of Notch mutations in a large panel of cancer cell lines in silico.
  
  
  RESULTS
  Our results show that the mutation frequency of Notch receptor and ligand genes is at par with that for established oncogenes and higher than for a set of house-keeping genes. Mutations were found across all four Notch receptor genes, but with notable differences between protein domains, mutations were for example more prevalent in the regions encoding the LNR and PEST domains in the Notch intracellular domain. Furthermore, an in silico estimation of functional impact showed that deleterious mutations cluster to the ligand-binding and the intracellular domains of NOTCH1. For most cell line groups, the mutation frequency of Notch genes is higher than in associated primary tumors.
  
  
  CONCLUSIONS
  Our results shed new light on the spectrum of Notch mutations after in vitro culturing of tumor cells. The higher mutation frequency in tumor cell lines indicates that Notch mutations are associated with a growth advantage in vitro, and thus may be considered to be driver mutations in a tumor cell line context.
authors.affiliation: Department of Cell and Molecular Biology, SE-171 77, Stockholm, Sweden. anm2132@med.cornell.edu.
authors.forename: Anders Peter
authors.initials: AP
authors.lastname: Mutvei
authors.affiliation: Department of Oncology and Pathology, Science for Life Laboratory, Karolinska Institute, SE-171 77, Stockholm, Sweden. erik.fredlund@ki.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Fredlund
authors.affiliation: Department of Cell and Molecular Biology, SE-171 77, Stockholm, Sweden. urban.lendahl@ki.se.
authors.forename: Urban
authors.initials: U
authors.lastname: Lendahl
mesh_terms: D045744:Cell Line, Tumor; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020043:Genes, Essential; D006801:Humans; D020125:Mutation, Missense; D051880:Receptors, Notch / Q000235:genetics*
chemical_list: D051880:Receptors, Notch