Targeted next-generation sequencing reveals genomic differences between male and female breast cancer

靶向二代测序揭示男性和女性乳腺癌的基因组差异

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Abstract

BACKGROUND: Compared with female breast cancer (FBC), male breast cancer (MBC) is often detected at the advanced stage and has a poorer prognosis. Due to the limited research data on MBC, its clinical diagnosis and treatment regimens are mainly based on FBC, although these regimens may not be appropriate for MBC patients. This study aimed to investigate the similarities and differences between MBC and FBC at the genetic level, in order to provide ideas and basis for the diagnosis and treatment of MBC. METHODS: In this cross-sectional study, we conducted high-throughput sequencing on formalin-fixed paraffin-embedded (FFPE) samples obtained from a cohort of 12 MBC and 14 FBC patients. Utilizing bioinformatics tools, we meticulously analyzed and compared the genomic profiles to elucidate the underlying genetic distinctions between MBC and FBC. RESULTS: In our study, MLL3 and GATA3 mutations were most prevalent in MBC while TP53, PIK3CA and MLL3 mutations dominated in FBC. Notably, certain genes exhibited shared point mutations and copy number variations (CNVs) across genders. The mutation prevalence of PIK3CA was significantly different between MBC and FBC. CDK12 and ERBB2 had the highest prevalence of CNV in FBC, contrasting with their absence in MBC. Both in MBC and FBC, MYC had the highest prevalence in CNV. Furthermore, FBC demonstrated a higher tumor mutational burden (TMB) than MBC. MBC private genes were involved in a variety of disease-related signaling pathways, with the ErbB and PI3K-Akt pathways being significantly enriched. CONCLUSIONS: We concluded that MBC and FBC exhibit both genomic similarities and distinctions in our study. In the context of precision medicine, this study may provide new ideas and a basis for the diagnosis and treatment of MBC.

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