PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas

Hafner, Christian ; Schmiemann, Viola ; Ruetten, Arno ; Coras, Brigitte ; Landthaler, Michael ; Reifenberger, Julia ; Vogt, Thomas

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Trichoblastomas are rare, benign tumors of the appendix in human skin. The histopathology comprises elements of basal cell carcinoma and trichoepithelioma with a variable degree of follicular differentiation. Both basal cell carcinoma and trichoepithelioma reveal alterations of PTCH, the human homolog of the Drosophila segment polarity patched gene. Furthermore, heterozygous PTCH knockout mice develop trichoblastoma-like tumors. This suggests an involvement of the PTCH gene in the pathogenesis of human trichoblastomas. However, trichoblastomas arising in nevus sebaceus did not show loss of heterozygosity at the PTCH locus (9q22.3) in a previous study. Sequencing of the PTCH gene and analysis of sporadic human trichoblastomas have not been performed yet. We therefore screened 10 sporadic trichoblastomas and I trichoblastorna arising within a nevus sebaceus for PTCH mutations. After microdissection of the tumors, single-strand conformational polymorphism (SSCP)/ heteroduplex analysis of exons 2 to 23 of PTCH was performed, and polyrnerase chain reaction products with aberrant band patterns were sequenced. One trichoblastorna revealed a silent mutation at codon 562 in exon 12. Another trichoblastorna showed a somatic C > T single nucleotide substitution at codon 1315 (exon 23), which was not present in corresponding normal epidermis. This mutation at codon 1315 represents an already described PTCH germline polymorphism and results in a heterozygous Pro to Leu substitution in the tumor. The Pro/Leu polymorphism in germline is associated with a higher risk for breast cancer, but a potential contribution to the tumorigenesis of trichoblastorna is unknown. We detected no classical PTCH mutations in the investigated trichoblastomas. Our results indicate that PTCH mutations are not mainly involved in the pathogenesis of sporadic trichoblastomas, in contrast to basal cell carcinomas and trichoepitheliomas. The genetic basis of this rare appendageal tumor remains elusive. (c) 2007 Elsevier Inc. All rights reserved.

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