Τετάρτη 18 Νοεμβρίου 2020

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis in childhood: a genetic and epigenetic study with comparison with basal cell carcinomas evolving in chronically sun‐exposed areas

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Abstract

Background

Basal cell carcinoma (BCC) has been mostly associated with sun‐exposure, but ionizing radiation is also a known risk factor. It is not clear if the pathogenesis of BCC, namely at a genomic and epigenetic level, differs according to the underlying triggering factors.

Objective

The present study aims to compare genetic and epigenetic changes in BCCs related to ionizing radiation and chronic sun‐exposure.

Methods

Tumour samples from BCCs of the scalp in patients submitted to radiotherapy to treat tinea capitis in childhood and BCCs from sun‐exposed areas were analysed through array comparative genomic hybridization (array‐CGH) and methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) to detect copy number alterations and methylation status of specific genes.

Results

Genomic characterization of tumour samples revealed several copy number gains and losses in all chromosomes, with the most frequent gains observed at 2p, 6p, 12p, 14q, 15q, 18q, Xp and Yp, and the most frequent losses observed at 3q, 14q, 16p, 17q, 22q, Xp, Yp and Yq. We developed a statistical model, encompassing gains in 3p and 16p and losses in 14q and 20p, with potential to discriminate BCC samples with sporadic aetiology from BCC samples that evolve after radiotherapy in childhood for the treatment of tinea capitis, which presented statistical significance (p = 0.003). Few methylated genes were detected through MS‐MLPA, most frequently RARB and CD44.

Conclusions

Our study represents a step forward in the understanding of the genetic mechanisms underlying the pathogenesis of BCC and suggests potential differences according to the underlying risk factors.

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