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Genetic mosaicism in basal cell carcinoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2005 (English)In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 14, no 8, 593-600 p.Article in journal (Refereed) Published
Abstract [en]

Human basal cell cancer (BCC) shows unique growth characteristics, including a virtual inability to metastasize, absence of a precursor stage and lack of tumour progression. The clonal nature of BCC has long been a subject for debate because of the tumour growth pattern. Despite a morphologically multifocal appearance, genetic analysis and three-dimensional reconstructions of tumours have favoured a unicellular origin. We have utilized the X-chromosome inactivation assay in order to examine clonality in 13 cases of BCC. Four parts of each individual tumour plus isolated samples of stroma were analysed following laser-assisted microdissection. In 12/13 tumours, the epithelial component of the tumour showed a monoclonal pattern suggesting a unicellular origin. Surprisingly, one tumour showed evidence of being composed of at least two non-related monoclonal clones. This finding was supported by the analysis of the ptch and p53 gene. Clonality analysis of tumour stroma showed both mono- and polyclonal patterns. A prerequisite for this assay is that the extent of skewing is determined and compensated for in each case. Owing to the mosaic pattern of normal human epidermis, accurate coefficients are difficult to obtain; we, therefore, performed all analyses both with and without considering skewing. This study concludes that BCC are monoclonal neoplastic growths of epithelial cells, embedded in a connective tissue stroma at least in part of polyclonal origin. The study results show that what appears to be one tumour may occasionally constitute two or more independent tumours intermingled or adjacent to each other, possibly reflecting a local predisposition to malignant transformation.

Place, publisher, year, edition, pages
2005. Vol. 14, no 8, 593-600 p.
Keyword [en]
Carcinoma; Basal Cell/*genetics/metabolism, Cell Transformation; Neoplastic, Chromosome Aberrations, Chromosomes; Human; X, DNA/metabolism, Disease Progression, Dosage Compensation; Genetic, Epidermis/metabolism, Epithelium/metabolism, Female, Heterozygote, Humans, Lasers, Loss of Heterozygosity, Mosaicism, Neoplasms; Glandular and Epithelial/*genetics/metabolism, Receptors; Androgen/*genetics, Research Support; Non-U.S. Gov't, Tumor Suppressor Protein p53/metabolism
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-93046DOI: 10.1111/j.0906-6705.2005.00333.xPubMedID: 16026581OAI: oai:DiVA.org:uu-93046DiVA: diva2:166404
Available from: 2005-05-11 Created: 2005-05-11 Last updated: 2013-03-21Bibliographically approved
In thesis
1. Molecular Analysis of Normal Human Skin and Basal Cell Carcinoma Using Microdissection Based Methods
Open this publication in new window or tab >>Molecular Analysis of Normal Human Skin and Basal Cell Carcinoma Using Microdissection Based Methods
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this thesis was to gain further insight into the biology of normal human skin and basal cell carcinoma (BCC). Morphology in combination with microdissection was used as primary tool for sampling.

Using the X-chromosome inactivation assay, we found normal human skin to consist of a mosaic of cells, with either the maternal or the paternal X-chromosome inactivated. We believe that each tile is made up of several epidermal proliferative units with identical X-chromosome inactivation patterns. Using the same method, we found BCC to be a monoclonal neoplasm imbedded in polyclonal stroma. However, one tumor displayed clear evidence of being composed of two intermingled monoclonal tumors.

To better enable molecular analysis of defined cells from tissue sections, we investigated a zinc-based fixative as alternative to neutral-buffered formalin. Zinc-based fixative preserves good quality of genomic DNA, with only slight impairment of morphology. In addition, it partly abrogates the need for antigen retrieval.

The patched gene is involved in BCC development. We analyzed the distribution of a coding polymorphism (Pro/Leu) at codon 1315 in populations with different skin types. We found a reduced Pro/Pro genotype frequency in populations with lighter pigmentation. This in combination with genotype analyses of patients with multiple BCCs, showed that failure to lose the Pro allele during a shift towards lighter pigmented skin may be associated with an increased risk of developing BCC.

We compared the expression profile of BCC cells with putative progenitor cells in the basal layer of epidermis. In addition to discovering several unknown genes, we found the Wnt signaling pathway to upregulated. Furthermore, differentiation markers were downregulated together with proteins important for scavenging of oxygen radicals.

In conclusion, the combination of morphology, microdissection and subsequent molecular applications provided valid information deepening our understanding of normal skin and BCC.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 50 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 40
Pathology, skin, basal cell carcinoma, microdissection, X-chromosome inactivation, Patologi
National Category
Cell and Molecular Biology
urn:nbn:se:uu:diva-5795 (URN)91-554-6249-9 (ISBN)
Public defence
2005-05-28, Rudbecksalen, Rudbecklaboratoriet C11, Dag Hammarskjöldsväg 20, Uppsala, 09:15
Available from: 2005-05-11 Created: 2005-05-11Bibliographically approved

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