GENE EXPRESSION AND SOMATIC MUTATION PROFILES ACROSS MOLECULAR SUBTYPES OF BREAST CANCER

Sarah N. Namusoke; Joseph K. Mugisha; Esther A. Nakato

doi:10.69980/bs.v12i2.6809

Sarah N. Namusoke Department of Biochemistry, Makerere University, Kampala, Uganda
Joseph K. Mugisha Department of Pathology, Makerere University, Kampala, Uganda
Esther A. Nakato Department of Biological Sciences, Mbarara University of Science and Technology, Mbarara, Uganda

DOI: https://doi.org/10.69980/bs.v12i2.6809

Keywords: Breast cancer, Gene expression, Somatic mutation, Molecular subtype, METABRIC

Abstract

Breast cancer is a molecularly heterogeneous disease characterized by distinct gene-expression patterns and somatic alterations across intrinsic subtypes. Integrated assessment of transcriptomic and genomic features can improve understanding of subtype-specific tumor biology. A retrospective secondary-data analysis was conducted using 1,898 breast cancer cases classified as Luminal A, Luminal B, HER2-enriched, Basal, Claudin-low, or Normal-like. Gene-expression differences were evaluated using the Kruskal–Wallis test, while mutation–subtype associations were assessed using chi-square or Fisher’s exact tests. Mann–Whitney U testing was used to compare expression between mutation-positive and mutation-negative groups, with false discovery rate correction applied for multiple testing. Significant subtype-associated expression differences were identified, with GATA3, EGFR, MAPT, AURKA, CCNE1, CHEK1, IGF1R, CDC25A, CDK1, and E2F2 among the most strongly differentiated genes. PIK3CA and TP53 were the most frequently mutated genes, while TP53, PIK3CA, GATA3, MAP3K1, CDH1, and other alterations showed significant subtype associations. Mutation status was also linked with corresponding expression changes for several genes, including CDH1, GATA3, AKT1, PTEN, TP53, MAP3K1, and ERBB2. Integrated transcriptomic and genomic profiling revealed marked molecular heterogeneity across breast cancer subtypes and highlighted potentially important subtype-associated biomarkers.

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GENE EXPRESSION AND SOMATIC MUTATION PROFILES ACROSS MOLECULAR SUBTYPES OF BREAST CANCER

Abstract

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