Molecular alterations in basal cell carcinoma subtypes.

Area of Science:

• Oncology
• Molecular Biology
• Dermatology

Background:

• Basal cell carcinoma (BCC) pathogenesis involves the Hedgehog pathway and other genetic alterations.
• Understanding these molecular changes is crucial for developing targeted therapies.

Purpose of the Study:

• To comprehensively analyze mutations in 13 key BCC-related genes in superficial and nodular BCC.
• To identify associations between specific gene mutations and BCC subtypes, clinical features, and potential risk factors.

Main Methods:

• In-depth genetic analysis of 13 BCC-related genes (CSMD1, CSMD2, DPH3 promoter, PTCH1, SMO, GLI1, NOTCH1, NOTCH2, TP53, ITIH2, DPP10, STEAP4, TERT promoter).
• Analysis was performed on 57 BCC lesions (26 superficial, 31 nodular) from 55 patients and their corresponding blood samples.

Main Results:

• High mutation rates observed in PTCH1 (71.9%), TP53 (45.6%), CSMD1 (63.2%), NOTCH1 (43.8%), DPP10 (35.1%), TERT promoter (57.9%), and DPH3 promoter (49.1%).
• CSMD1 mutations co-occurred with TP53 changes (p=0.002).
• Superficial BCC showed significant associations with PTCH1 (p=0.018) and NOTCH1 (p=0.020) mutations.
• PTCH1 mutations linked to intermittent sun exposure (p=0.046) and single lesions (p=0.021).
• NOTCH1 mutations were more frequent in BCCs on the trunk (p=0.001).

Conclusions:

• This study provides detailed molecular insights into superficial and nodular BCC development.
• Identified genetic alterations and their associations can inform novel, rationale-based therapeutic strategies for BCC.