Pathway Mutations in Breast Cancer Using Whole-Exome Sequencing

Area of Science:

• Genomics
• Oncology
• Molecular Biology

Background:

• The genomic landscape of breast cancer (BC) is intricate and varies across populations.
• Understanding specific mutational profiles is crucial for effective treatment strategies.

Purpose of the Study:

• To elucidate the mutational landscape of breast cancer in Taiwanese patients.
• To identify novel genetic variants and their association with clinical outcomes.

Main Methods:

• Whole-exome sequencing of 24 tumor tissue specimens.
• Sanger sequencing for variant validation and analysis of paired nontumor tissues.
• Genotype calling, annotation, and molecular subtype classification.

Main Results:

• Identified 49 deleterious variants in canonical cancer-related genes, with PIK3CA, FKBP9, and TP53 being the most frequent.
• Discovered seven novel mutations not previously recorded in mutation databases.
• Found distinct pathway alterations across molecular subtypes (luminal A, luminal B, basal-like).
• MAPK signaling pathway and endocytosis mutations were associated with poor prognosis, confirmed by cBioPortal analysis.

Conclusions:

• This research reveals novel mutations and subtype-specific alterations in Taiwanese breast cancer patients.
• Findings support the development of targeted therapies and personalized treatment approaches for breast cancer.