Coding and noncoding somatic mutations in basal cell carcinoma

Basal cell carcinoma (BCC) represents the most commonly diagnosed human cancer among persons of European ancestry with etiology mainly attributed to sun-exposure. In this study we investigated mutations in coding and flanking regions of the and genes and noncoding alterations in the and promoters in 191 BCC tumors. In addition, we measured CpG methylation within the hypermethylated oncological region (THOR) and transcriptions levels of the reverse transcriptase subunit. We observed mutations in in 59% and in 31% of the tumors. Noncoding mutations in and promoters were detected in 59% and 38% of the tumors, respectively. We observed a statistically significant co-occurrence of mutations at the four investigated loci. While mutations tended to associate with decreased patient age at diagnosis; mutations were associated with light skin color and increased number of nevi; and promoter with history of cutaneous neoplasms in BCC patients. promoter mutations but not THOR methylation associated with an increased expression of the reverse transcriptase subunit. Our study signifies, in addition to the protein altering mutations in the and genes, the importance of noncoding mutations in BCC, particularly functional alterations in the promoter.