Coding and noncoding somatic mutations in candidate genes in basal cell carcinoma.

Area of Science:

• Oncology
• Genetics
• Dermatology

Background:

• Basal cell carcinoma (BCC) is the most common human cancer in fair-skinned populations, primarily linked to sun exposure.
• Understanding the genetic underpinnings of BCC is crucial for improving diagnosis and treatment strategies.

Purpose of the Study:

• To investigate both coding and noncoding mutations in key genes (PTCH1, TP53, TERT, DPH3) in 191 BCC tumors.
• To explore the correlation between specific mutations, clinical features, and gene expression levels.

Main Methods:

• Genomic analysis of PTCH1, TP53, TERT, and DPH3 in 191 BCC tumors.
• Assessment of TERT hypermethylated oncological region (THOR) methylation and reverse transcriptase subunit expression.

Main Results:

• High frequencies of mutations were observed in PTCH1 (58.6%), TP53 (31.4%), TERT promoter (59.2%), and DPH3 promoter (38.2%).
• Significant co-occurrence of mutations across the four loci was noted.
• PTCH1 mutations correlated with younger age at diagnosis; TP53 with lighter skin and nevi; TERT/DPH3 promoters with prior skin neoplasms.
• TERT promoter mutations, not THOR methylation, were linked to increased reverse transcriptase subunit expression.

Conclusions:

• Noncoding mutations in TERT and DPH3 promoters play a significant role in BCC pathogenesis, comparable to coding mutations in PTCH1 and TP53.
• Functional alterations in the TERT promoter are particularly important in BCC development.