Transcription Factors in Breast Cancer-Lessons From Recent Genomic Analyses and Therapeutic Implications

Area of Science:

• Genomics
• Molecular Biology
• Cancer Research

Background:

• Multiplatform genomic analyses reveal frequent alterations in breast cancer (BC).
• Approximately 49 of 93 frequently altered genes in BC are involved in transcription.
• These include DNA-binding transcription factors (DB-TFs), coregulators, and epigenetic modifiers.

Purpose of the Study:

• To review diverse oncogenic alterations in transcription factors (TFs) in breast cancer.
• To discuss the implications of these TF alterations for therapeutic strategies.

Main Methods:

• Multiplatform genomic analyses to identify frequently altered genes in breast cancer.
• G:profiler analysis to assess affected pathways.
• Review of existing literature on TF alterations in breast cancer.

Main Results:

• 49 transcription-related genes are frequently altered in BC, affecting cell cycle, development, steroid hormone, and chromatin modification pathways.
• Unlike oncogenic signaling TFs, corepressors or upstream regulators are lost, or coactivators are induced.
• Constitutive and signal-induced DB-TFs not mediating default repression are directly altered.
• Mutations in regulatory elements and chromatin conformation create new TF-binding sites, promoting oncogenesis.

Conclusions:

• Breast cancer pathogenesis involves complex dysregulation of transcription, including alterations in TFs and regulatory elements.
• Understanding these TF alterations is crucial for developing targeted BC therapies.