Gene Fusion-Driven Cutaneous Adnexal Neoplasms: An Updated Review Emphasizing Molecular Characteristics.

Area of Science:

• Oncology
• Molecular Biology
• Dermatopathology

Background:

• Gene rearrangements and fusions are increasingly recognized as critical oncogenic drivers in cutaneous adnexal neoplasms.
• A diverse range of molecular alterations underlies the pathogenesis of these tumors.

Purpose of the Study:

• To provide a comprehensive review of established and novel molecular alterations, focusing on gene fusions in cutaneous adnexal tumors.
• To highlight the significance of these genetic changes in tumor biology and their therapeutic implications.

Main Methods:

• Literature review of established and recent studies on gene fusions in cutaneous adnexal neoplasms.
• Analysis of key molecular alterations including YAP1, CRTC1::MAML2, BRD3, MYB::NFIB, ETV6::NTRK3, PLAG1, and rarer fusion transcripts.

Main Results:

• Key gene fusions like YAP1, CRTC1::MAML2, MYB::NFIB, and ETV6::NTRK3 are significant drivers.
• Rarer fusions such as MEF2C::SS18 and FOXK1::GRHL1/2 also contribute to tumor development.
• These genetic alterations impact tumor biology and present therapeutic targets.

Conclusions:

• Gene fusions are pivotal in the oncogenesis of cutaneous adnexal tumors.
• Understanding these molecular drivers is crucial for diagnosis and developing targeted therapies for advanced and metastatic disease.