PTCH2, a novel human patched gene, undergoing alternative splicing and up-regulated in basal cell carcinomas.
(1/1029)
By a combination of cDNA library screening, rapid amplification of cDNA ends analysis, and BAC sequencing, a novel human patched-like gene (PTCH2) has been cloned and sequenced. The genomic organization is similar to PTCH1 with 22 exons and, by radiation hybrid mapping, PTCH2 has been localized to chromosome 1p33-34, a region often lost in a variety of tumors. Several alternatively spliced mRNA forms of PTCH2 were identified, including transcripts lacking segments thought to be involved in sonic hedgehog binding and mRNAs with differentially defined 3' terminal exons. In situ hybridization revealed high expression of PTCH2 transcripts in both familial and sporadic basal cell carcinomas in similarity to what has been observed for PTCH1, suggesting a negative regulation of PTCH2 by PTCH1. This finding tightly links PTCH2 with the sonic hedgehog/PTCH signaling pathway, implying that PTCH2 has related, but yet distinct, functions than PTCH1. (+info)
Optimum porphyrin accumulation in epithelial skin tumours and psoriatic lesions after topical application of delta-aminolaevulinic acid.
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Photodynamic therapy with topically applied delta-aminolaevulinic acid is used to treat skin tumours by employing endogenously formed porphyrins as photosensitizers. This study examines the time course of porphyrin metabolite formation after topical application of delta-aminolaevulinic acid. Porphyrin biosynthesis in human skin tumours (basal cell carcinoma, squamous cell carcinoma), in psoriatic lesions, and in normal skin was investigated. Skin areas were treated with delta-aminolaevulinic acid, and levels of total porphyrins, porphyrin metabolites and proteins were measured in samples excised after 1, 2, 4, 6, 9, 12 and 24 h. There was an increase in porphyrin biosynthesis in all tissues with maximum porphyrin levels in tumours between 2 and 6 h and in psoriatic lesions 6 h after treatment. The pattern of porphyrins showed no significant difference between normal and neoplastic skin, protoporphyrin being the predominant metabolite. The results suggest that optimum irradiation time for superficial epithelial skin tumours may be as soon as 2 h after application of delta-aminolaevulinic acid, whereas for treatment of psoriatic lesions an application time of 6 h is more suitable. (+info)
A man with a prosthetic ear and multiple pulmonary nodules.
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Basal cell carcinoma is generally regarded as a relatively indolent tumor easily controlled with local therapy. When neglected or inadequately treated this tumor can become locally aggressive and in rare circumstances metastasize. This report documents a case of basal cell carcinoma metastatic to the lung that resulted in rapidly progressive respiratory failure and death. (+info)
Color Doppler sonography of focal lesions of the skin and subcutaneous tissue.
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We evaluated with color Doppler sonography 71 visible and palpable nodules of the skin and subcutaneous tissue from 51 patients. The nodules were classified as avascular (type I), hypovascular with a single vascular pole (type II), hypervascular with multiple peripheral poles (type III), and hypervascular with internal vessels (type IV). Of the 32 malignant nodules, 9% showed a type I pattern, 50% had a type III pattern, and 41% had a type IV pattern; of the 39 benign nodules, 86% showed a type I pattern and 14% had a type II pattern. The sensitivity and specificity of hypervascularity in malignant lesions were 90% and 100%, respectively, whereas the sensitivity and specificity of hypovascularity in benign lesions were 100% and 90%, respectively. The authors conclude that color Doppler sonography is able to increase the specificity of ultrasonography in the evaluation of nodular lesions of the skin. (+info)
Long-term results after surgical basal cell carcinoma excision in the eyelid region.
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AIMS: To evaluate the data for patients with basal cell carcinoma (BCC) in the eyelid region, to demonstrate histologically controlled tumour excision, and to prove the efficacy of the treatment on the basis of long term observations. METHODS: Retrospective analysis of 382 microscopically controlled BCC excisions in the eyelid apparatus (350 patients) in a follow up study over 5.7 (SD 1.1) years. Tumour location, tumour size, and histological results were recorded. The same procedure was followed for recurrences. Follow up examinations were carried out 1, 3, 6, and 12 months after the operation, and then annually for a further 4 years or longer. RESULTS: A recurrence rate of 5.36% was observed after the primary operation. 60.3% of first recurrences occurred in the medial canthus, 41.2% showed in depth extension, and sclerosing types were overly represented at 35.3%. After the second operation the recurrence rate increased to 14.7% and reached 50% after a third and fourth operation. CONCLUSIONS: The greatest risk of recurrence exists for BCCs of the medial canthus with in depth extension, and for sclerosing types. The recurrence rate increases after every operation. For high risk cases, consideration should be given to adjuvant treatment such as radiotherapy. (+info)
The sebaceous nevus: a nevus with deletions of the PTCH gene.
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Sebaceous nevi (SN) are congenital malformations of the skin with the potential to develop into basal cell carcinoma (BCC). To date, the molecular basis for their carcinogenic potential remains unknown. The genetic defect in BCC is known and involves the human homologue of Drosophila patched (PTCH) on chromosome 9q22.3. The objective of this study was to test whether allelic deletion of the PTCH gene could already be detected in SN. Twenty-one paraffin-embedded SN were investigated in this study. Basaloid cells in conjunction with mature sebaceous glands as well as epidermal layer apart from SN were microdissected and subjected to single-step DNA extraction. We performed the analysis with polymorphic markers at 9q22.3 (D9S15, D9S252, D9S287, and D9S303). Of the 20 informative SN, 8 (40%) exhibited loss of heterozygosity at least at one locus. Here, we provide the first evidence of the involvement of the tumor suppressor gene PTCH in SN. Whether PTCH deletion in SN is associated with progression to BCC and/or other appendageal tumors should be addressed in future studies. (+info)
High levels of patched gene mutations in basal-cell carcinomas from patients with xeroderma pigmentosum.
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Recently, hptc, a human gene homologous to the Drosophila segment polarity gene patched (ptc), has been implicated in the nevoid basal-cell carcinoma (BCC) syndrome, and somatic mutations of hptc also have been found in sporadic BCCs, the most frequent cancers found in the white population. We have analyzed the hptc gene, postulated to be a tumor suppressor gene, in 22 BCCs from patients with the hyperphotosensitive genodermatosis xeroderma pigmentosum (XP). Patients with XP are deficient in the repair of UV-induced DNA lesions and are characterized by their predisposition to cancers in sun-exposed skin. Analysis using PCR-single-strand conformation polymorphism of the hptc gene identified 19 alterations in 16 of 22 (73%) of the BCCs examined. Only two (11%) deletions of the hptc gene were found in XP BCCs compared with >30% rearrangement observed in non-XP sporadic BCCs, and 17 of 19 (89%) were base substitutions. Among the 17 base substitutions, 11 (65%) were CC --> TT tandem mutations, and 4 (23%) were C --> T substitutions, all targeted at bipyrimidine sites. Hence, a significantly higher number (15 of 19; 79%) of UV-specific alterations are seen in XP tumors, in contrast to non-XP sporadic BCCs. Interestingly, we have found that in 7 of 14 (50%) XP BCCs analyzed, both hptc and the tumor suppressor gene p53 are mutated. Not only have our data indicated the key role played by hptc in the development of BCCs, they also have substantiated the link between unrepaired UV-induced DNA lesions and skin carcinogenesis, as exemplified by the UV-specific alterations of different genes in the same tumors. (+info)
Mutational spectrum of p53 gene in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan.
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To understand the role of p53 tumour suppressor gene in the carcinogenesis of arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan, we collected tumour samples from 23 patients with Bowen's disease, seven patients with basal cell carcinomas (BCC) and nine patients with squamous cell carcinomas (SCC). The result showed that p53 gene mutations were found in 39% of cases with Bowen's disease (9/23), 28.6% of cases with BCC (2/7) and 55.6% of cases with SCC (5/9). Most of the mutation sites were located on exon 5 and exon 8. Moreover, the results from direct sequencing indicated that missense mutations were found at codon 149 (C-->T) in one case, codon 175 (G-->A) in three cases, codon 273 (G-->C) in three cases, codon 292 (T-->A) in one case, codon 283 (G-->T) in one case, codon 172 (T-->C) in one case and codon 284 (C-->A) in one case. In addition, silent mutations were also found in four cases. These mutations were located at codons 174, 253, 289 and 298 respectively. In immunohistochemistry analysis, p53 overexpression was found in 43.5% (10/23) of cases with Bowen's disease, 14% (1/7) of cases with BCC and 44% (4/9) of cases with SSC. These findings showed that p53 gene mutation rate in arsenic-related skin cancers from the blackfoot disease endemic area of Taiwan is high and that the mutation types are different from those in UV-induced skin cancers. (+info)