Molecular characterization of aggressive basal cell carcinoma

Abstract

A subset of Basal Cell Carcinoma (BCC) tumors characterized by rapid growth, recurrence, deep local invasiveness including dura and/or bone is classified as aggressive. These tumors are histologically similar to the non‐aggressive BCC. We have compared molecular signatures of these tumors.21 BCC specimens, 6 aggressive and 15 non‐aggressive were used in the study. DNA was extracted from formalin fixed paraffin embedded sections of 21 pairs of normal and tumor tissue. The specimens were subjected to Loss of Heterozygosity (LOH) analysis in the PATCHED gene using capillary electrophoresis, single nucleotide polymorphisms (SNP's) in cytokine promoter genes by real‐time PCR and melt curve analysis, UV specific mutations in the Sonic Hedgehog (SHH) gene and the V600E mutation in the BRAF kinase gene by sequencing and allele specific Taqman probes.Significant LOH was observed in 54.5% of the aggressive BCC compared to 17.9% of the non‐aggressive BCC. The TNF‐a ‐238 SNP was more prevalent in aggressive (3/6) compared to non‐aggressive BCC (3/12). There was a greater incidence of the IL‐10 ‐1082 SNP ‐ 4/6 in aggressive versus 6/16 in the non‐aggressive BCC. No mutation in the BRAF kinase gene was detected and none of the specimens had mutations in the SHH gene.Our results indicate an increase in LOH in aggressive BCC compared to non‐aggressive specimens and suggest that aggressive BCC prefer a pro‐inflammatory environment.