Abstract
Familial predisposition to basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin are apparent in the autosomal dominant syndromes naevoid basal cell carcinoma syndrome (NBCCS) and multiple self-healing squamous epitheliomata (MSSE) respectively. The gene responsible for NBCCS has been proposed to be a tumour-suppressor gene and is mapped to the same 2 Mb interval on 9q22.3 as the MSSE gene ESS1. In an attempt to further map the NBCCS gene, we have examined loss of heterozygosity (LOH) in 16 sporadic BCCs and two familial BCCs using microsatellite markers located within the candidate gene region. The overall frequency of LOH observed was 67% in the BCCs and partial or interstitial deletions were found in eight tumours, with the highest LOH frequency at markers D9S280, D9S287 and D9S180. To determine if the same genomic region also shows frequent LOH in tumours with a squamous phenotype, we have examined 11 SCCs, four actinic keratoses and 13 cases of Bowen's disease for LOH at 9q22.3. An overall LOH frequency of 50% was observed at D9S180, and occurred in all types of squamous tumours. In contrast, a much lower LOH frequency of only 6% was found at the D9S287 locus. Our observation of different patterns of LOH at 9q22.3 in sporadic BCCs and SCCs implies that more than one tumour-suppressor gene might be located in this genomic region.
Highlights
In order to confirm the frequent loss of the 9q22.3 area by loss of heterozygosity (LOH) in basal cell carcinoma (BCC) and to further map the naevoid basal cell carcinoma syndrome (NBCCS) gene region, we have examined sporadic and familiar BCCs for the occurrence of LOH using microsatellite markers located within the candidate area
To test the hypothesis that a gene in the same chromosomal area may be involved in the development of the squamous type of skin tumours we have investigated the frequency of 9q22.3 loss in squamous cell carcinoma (SCC), and in the premalignant skin lesions actinic keratoses and Bowen's disease
Eighteen BCCs, 11 SCCs, four actinic keratoses and 13 cases of Bowen's disease were examined for LOH on chromosome 9q22.3, a region to which the NBCCS and ESSI gene(s) have been located
Summary
Sixteen sporadic BCCs, two BCCs from a patient with NBCCS, 11 SCCs, four actinic keratoses, and 13 cases of Bowen's disease were studied. Before DNA extraction paraffin was removed by adding 100 jAl of NIB buffer (0.45% NP40, 0.45% TWEEN 20, 50 mM potassium chloride, 10 mM Tris pH 8.3, 1.5 mm magnesium chloride and 100 ,ug ml-I gelatine) to the sample and boiling for 20 min followed by a 10 min centrifugation at 13 000 r.p.m. The supernatant was removed and used for further processing. Detection of loss of heterozygosity Four microsatellite markers from the putative NBCCS/ESSJ area on chromosome 9q22.3 (D9S196, D9S280, D9S287, D9S180) were used to genotype the tumours and corresponding normal tissue using the polymerase chain reaction (PCR). The PCR products were analysed on 6% polyacrylamide denaturing gels in 1 x TBE buffer in an ABI 373A automated DNA sequencer (Applied Biosystems, Foster City, CA, USA), and subsequently analysed by Genescan 672 (Applied Biosystems, Foster City, CA, USA) for size, peak height and peak area.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
