Metaplastic breast carcinomas display genomic and transcriptomic heterogeneity [corrected].

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Metaplastic breast carcinoma is a rare, aggressive cancer, often triple-negative.
• Understanding its transcriptomic heterogeneity is crucial for targeted therapies.
• Previous classifications did not fully capture the molecular diversity.

Purpose of the Study:

• To define the transcriptomic heterogeneity of metaplastic breast carcinomas.
• To correlate gene expression and copy number profiles with histologic subtypes.
• To investigate potential associations with BRCA1-associated breast cancer profiles.

Main Methods:

• Gene expression and copy number profiling of 28 triple-negative metaplastic breast carcinomas.
• Utilized PAM50/claudin-low and TNBC website classifiers for molecular subtyping.
• Integrated gene expression and copy number data for comprehensive clustering.

Main Results:

• Histologic subtypes (spindle cell, squamous, chondroid) correlated with distinct molecular subtypes (claudin-low, basal-like, mesenchymal-like).
• Integrative clustering revealed specific associations between histology and molecular clusters.
• 31% of tumors displayed BRCA1-like genomic profiles, irrespective of histology or molecular subtype.

Conclusions:

• Metaplastic breast carcinoma's histologic diversity is mirrored at the transcriptomic level.
• Specific molecular subtypes are associated with distinct metaplastic histologic features.
• BRCA1-like profiles are present in a subset but not linked to a particular subtype.