Transcriptome of male breast cancer matched with germline profiling reveals novel molecular subtypes with possible clinical relevance

Veronica Zelli, Valentina Silvestri, Virginia Valentini, Agostino Bucalo, Piera Rizzolo, Ines Zanna, Simonetta Bianchi, Anna Coppa, Giuseppe Giannini, Laura Cortesi, Daniele Calistri, Maria Grazia Tibiletti, Stephen B. Fox, Kconfab, Domenico Palli, Laura Ottini

Research output: Contribution to journalArticlepeer-review


Male breast cancer (MBC) is a rare and understudied disease compared with female BC. About 15% of MBCs are associated with germline mutation in BC susceptibility genes, mainly BRCA1/2 and PALB2. Hereditary MBCs are likely to represent a subgroup of tumors with a peculiar phenotype. Here, we performed a whole transcriptome analysis of MBCs characterized for germline mutations in the most relevant BC susceptibility genes in order to identify molecular subtypes with clinical relevance. A series of 63 MBCs, including 16 BRCA2, 6 BRCA1, 2 PALB2, 1 RAD50, and 1 RAD51D germline-mutated cases, was analyzed by RNA-sequencing. Differential expression and hierarchical clustering analyses were performed. Module signatures associated with central biological processes involved in breast cancer pathogenesis were also examined. Different transcriptome profiles for genes mainly involved in the cell cycle, DNA damage, and DNA repair pathways emerged between MBCs with and without germline mutations. Unsupervised clustering analysis revealed two distinct subgroups, one of which was characterized by a higher expression of immune response genes, high scores of gene-expression signatures suggestive of aggressive behavior, and worse overall survival. Our results suggest that transcriptome matched with germline profiling may be a valuable approach for the identification and characterization of MBC subtypes with possible relevance in the clinical setting.

Original languageEnglish
Article number4515
Issue number18
Publication statusPublished - Sept 2021


  • BRCA1/2
  • Germline mutations
  • Male breast cancer
  • Molecular subtypes
  • Transcriptome profiling

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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