Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International...

Area of Science:

• Genomics
• Oncology
• Molecular Biology

Background:

• Genomic alterations in cancer are crucial for diagnosis, prognosis, and therapeutic target discovery.
• Stage IV breast cancer (BC) presents complex genomic landscapes requiring detailed investigation.

Purpose of the Study:

• To identify clinically actionable genomic variants in stage IV breast cancer samples.
• To evaluate the utility of a BC-specific next-generation sequencing panel for variant detection.

Main Methods:

• DNA extraction from 41 formalin-fixed paraffin-embedded BC samples.
• Sequencing using MammaSeq, a BC-specific panel targeting 79 genes.
• Variant calling, annotation, and filtering for single nucleotide variants (SNVs) and copy number variations (CNVs).
• Clinical significance assessment using OncoKB and Precision Medicine Knowledgebase (PMKB).

Main Results:

• Sequencing of 41 stage IV BC samples identified 59 unique alterations (49 SNVs, 10 CNVs) across 38 genes.
• Eight alterations, including ERBB2, FGFR1, AR copy number gains and specific SNVs in IDH1, TP53, and PIK3CA, were deemed clinically significant.
• PIK3CA, TP53, MAP3K1, ATM, and NCOR1 were the most frequently mutated genes.

Conclusions:

• The study successfully identified clinically actionable genomic alterations in stage IV breast cancer.
• MammaSeq, a targeted next-generation sequencing panel, is effective for uncovering patient-specific genomic alterations.
• These findings support the use of targeted sequencing panels in clinical settings for improved breast cancer management.