Activation of a cryptic splice site of PTEN and loss of heterozygosity in benign skin lesions in Cowden disease

J. Trojan, G. Plotz, A. Brieger, J. Raedle, Stephen Meltzer, M. Wolter, S. Zeuzem

Research output: Contribution to journalArticle

Abstract

Cowden disease is an autosomal dominant syndrome characterized by facial trichilemmomas, acral keratoses, papillomatous papules, mucosal lesions, and an increased risk for breast and nonmedullary thyroid cancer. Here, we describe a novel PTEN splicing site mutation in a family with classical Cowden disease and we studied benign skin lesions typical for Cowden disease for loss of heterozygosity. We found a PTEN IVS2 + 1G > A 5′-splicing acceptor mutation resulting in activation of a cryptic splice site. Activation of this cryptic splice site is predicted to result in a frameshift with a premature stop codon, thus disrupting the phosphatase core motif of PTEN. Loss of heterozygosity analysis of two trichilemmomas, one fibroma, and three acanthomas of the index patient demonstrated loss of heterozygosity at the PTEN locus in four of these lesions. In conclusion, our data demonstrate that a PTEN splicing site mutation causes activation of a cryptic splice site, which results in aberrant transcripts.

Original languageEnglish (US)
Pages (from-to)1650-1653
Number of pages4
JournalJournal of Investigative Dermatology
Volume117
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Multiple Hamartoma Syndrome
RNA Splice Sites
Loss of Heterozygosity
Skin
Chemical activation
Mutation
Acanthoma
Keratosis
Fibroma
Nonsense Codon
Thyroid Neoplasms
Phosphoric Monoester Hydrolases
Breast
Extremities

Keywords

  • Genes, suppressor, tumor
  • Germline mutation
  • Hamartoma syndrome, multiple
  • Keratosis
  • Loss of heterozygosity
  • RNA splicing

ASJC Scopus subject areas

  • Dermatology

Cite this

Activation of a cryptic splice site of PTEN and loss of heterozygosity in benign skin lesions in Cowden disease. / Trojan, J.; Plotz, G.; Brieger, A.; Raedle, J.; Meltzer, Stephen; Wolter, M.; Zeuzem, S.

In: Journal of Investigative Dermatology, Vol. 117, No. 6, 2001, p. 1650-1653.

Research output: Contribution to journalArticle

Trojan, J. ; Plotz, G. ; Brieger, A. ; Raedle, J. ; Meltzer, Stephen ; Wolter, M. ; Zeuzem, S. / Activation of a cryptic splice site of PTEN and loss of heterozygosity in benign skin lesions in Cowden disease. In: Journal of Investigative Dermatology. 2001 ; Vol. 117, No. 6. pp. 1650-1653.
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AU - Meltzer, Stephen

AU - Wolter, M.

AU - Zeuzem, S.

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