title: beta-Catenin mutation and its nuclear localization are confirmed to be frequent causes of Wnt signaling pathway activation in pilomatricomas.
abstract: BACKGROUND
  beta-Catenin has been shown to play an important role in the formation of hair follicle-related tumors, including pilomatricomas. Several investigators have shown that beta-catenin gene mutation is observed in pilomatricomas. However, the relationship between the pattern of beta-catenin localization in the cell and beta-catenin gene mutation is still controversial.
  
  
  OBJECTIVE
  This work was performed to determine the frequency of beta-catenin nuclear localization in pilomatricoma, the relationship between the pattern of beta-catenin localization and beta-catenin mutation, and the involvement of APC mutation.
  
  
  METHODS
  Typical 32 pilomatricomas were examined for beta-catenin expression by immunostaining. Genomic DNA was extracted, amplified and sequenced from 23 pilomaticomas with nuclear beta-catenin staining and 4 pilomaticomas without nuclear beta-catenin staining. Mutations of beta-catenin gene were confirmed by subcloning assay and restriction endonuclease assay.
  
  
  RESULTS
  Using immunostaining, we found that 81% (26/32) of pilomatricomas displayed nuclear beta-catenin staining in basophilic cells. Sequence analysis revealed that 61% (14/23) contained mutations in exon 3 of beta-catenin. However, no mutations were detected in 4 pilomaticomas without beta-catenin nuclear staining. Detected mutations were adjacent to or abolished well-known regulatory phosphorylation sites of beta-catenin. APC gene mutations were not detected in 27 pilomatricomas with/without beta-catenin nuclear staining.
  
  
  CONCLUSIONS
  These results confirmed that beta-catenin mutation and its nuclear localization are frequent causes of Wnt signaling pathway activation and suggested that beta-catenin activation mutations contribute to tumorigenesis of pilomatricomas.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Xia
authors.forename: Kazunori
authors.initials: K
authors.lastname: Urabe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Moroi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Koga
authors.forename: Hong
authors.initials: H
authors.lastname: Duan
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D017491:Genes, APC; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018296:Pilomatrixoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D015398:Signal Transduction / Q000502:physiology*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin