beta-Catenin mutation and its nuclear localization are confirmed to be frequent causes of Wnt signaling pathway activation in pilomatricomas

J Dermatol Sci. 2006 Jan;41(1):67-75. doi: 10.1016/j.jdermsci.2005.09.005. Epub 2005 Dec 27.

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.

Objectives: 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.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Cell Nucleus / metabolism
  • Child
  • Child, Preschool
  • Exons / genetics
  • Female
  • Genes, APC
  • Hair Follicle / metabolism
  • Hair Follicle / pathology
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Pilomatrixoma / genetics*
  • Pilomatrixoma / metabolism
  • Pilomatrixoma / pathology
  • Point Mutation
  • Signal Transduction / physiology*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Wnt Proteins / metabolism*
  • beta Catenin / genetics*
  • beta Catenin / metabolism*

Substances

  • Wnt Proteins
  • beta Catenin