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Deregulation of the tumour suppressor genes p14ARF, p15INK4b, p16INK4a and p53 in basal cell carcinoma

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Abstract:

Summary Background 

Basal cell carcinoma (BCC) is a locally aggressive slowly growing tumour that rarely metastasizes and is mostly seen in older members of the population. Objectives 

To determine the involvement of the tumour suppressor genes p14ARF, p15INK4b, p16INK4a and p53 in BCC. Methods 

We investigated the integrity of the CDKN2A locus in 15 BCC samples by analysing the presence of allelic imbalance/loss of heterozygosity (LOH). Moreover, we studied the mRNA expression levels of the tumour suppressor genes p14ARF, p15INK4b, p16INK4a and p53 in the BCC samples and compared them with mRNA levels in the corresponding normal tissue. The presence of mutations was examined by sequencing for exons 1a and 2 of p16INK4a. Results 

We found LOH in one BCC sample for the marker D9S1748. A polymorphism (G442A) of exon 2 was detected in three cases. p14ARF, p15INK4b and p53 presented high expression levels, whereas p16INK4a exhibited low mRNA levels compared with the corresponding normal tissue. Significant correlations were detected among the genes studied. Conclusions 

Our results demonstrate a different expression profile between p16INK4a and p14ARF, p15INK4b and p53 in BCC. Moreover, we found a low percentage of LOH and of a polymorphic sequence variant (Ala148Thr) for the CDKN2A locus.

Keywords: basal cell carcinoma; mRNA expression; microsatellite instability/loss of heterozygosity; mutations; p14ARF; p15INK4b; p16INK4a; p53

Document Type: Research Article

DOI: https://doi.org/10.1111/j.1365-2133.2009.09079.x

Affiliations: A. Sygros Hospital, Department of Dermatology, Medical School, University of Athens, Athens, Greece

Publication date: 2009-06-01

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