Zelli Veronica, Silvestri Valentina, Valentini Virginia, Bucalo Agostino, Rizzolo Piera, Zanna Ines, Bianchi Simonetta, Coppa Anna, Giannini Giuseppe, Cortesi Laura, Calistri Daniele, Tibiletti Maria Grazia, Fox Stephen B, Fab kCon, Palli Domenico, Ottini Laura
Department of Molecular Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 08518 Florence, Italy.
Cancers (Basel). 2021 Sep 8;13(18):4515. doi: 10.3390/cancers13184515.
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 and . 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 6 , 2 , 1 , and 1 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.
与女性乳腺癌相比，男性乳腺癌（MBC）是一种罕见且研究不足的疾病。约15%的MBC与乳腺癌易感基因的种系突变有关，主要是 和 。遗传性MBC可能代表具有特殊表型的肿瘤亚组。在此，我们对在最相关的乳腺癌易感基因中具有种系突变特征的MBC进行了全转录组分析，以确定具有临床相关性的分子亚型。通过RNA测序分析了一系列63例MBC，包括16例 6 、2例 、1例 和1例种系突变病例。进行了差异表达和层次聚类分析。还检查了与乳腺癌发病机制中涉及的核心生物学过程相关的模块特征。在有和没有种系突变的MBC之间，出现了主要参与细胞周期、DNA损伤和DNA修复途径的基因的不同转录组谱。无监督聚类分析揭示了两个不同的亚组，其中一个亚组的特征是免疫反应基因表达较高、提示侵袭性行为的基因表达特征得分较高以及总生存率较差。我们的结果表明，与种系分析相匹配的转录组可能是一种有价值的方法，用于识别和表征在临床环境中可能相关的MBC亚型。
