A TRICHILEMMAL CARCINOMA ARISING FROM A PROLIFERATING TRICHILEMMAL CYST - THE LOSS OF THE WILD-TYPE P53 IS A CRITICAL EVENT IN MALIGNANT TRANSFORMATION

The genetic events responsible for tumor progression may be defined by careful analysis of genetic changes in well-chosen tumors which conta in distinct cell populations representing each stage of progression. H ere we report a case of a trichilemmal carcinoma arising in the wall o f a proliferating trichilemmal cyst (PTC). DNA was isolated from micro dissected areas of the PTC and the carcinoma respectively, and PCR-bas ed microsatellite loss of heterozygosity (LOH) analysis as well as P53 gene sequencing performed. A CGA to TGA nonsense mutation at codon 30 6 in exon 8 of the P53 gene was found in both samples, LOH analysis sh owed that the PTC retained chromosome arm 17p (where the p53 gene resi des), whereas the carcinoma was associated with the loss of this allel e. All the other loci examined were retained including 3p, 9q, 13q and 17q in both tumor parts. The results confirm a common clonal origin o f the PTC and the trichilemmal carcinoma, and strongly suggest that th e complete loss of the wild-type p53 is a critical event responsible f or malignant transformation in this particular case. Copyright (C) 199 8 by W.B. Saunders Company.