Al Saati Ayman, Vande Perre Pierre, Plenecassagnes Julien, Gilhodes Julia, Monselet Nils, Cabarrou Bastien, Lignon Norbert, Filleron Thomas, Telly Dominique, Perello-Lestrade Emilie, Feillel Viviane, Staub Anne, Martinez Mathilde, Chipoulet Edith, Collet Gaëlle, Thomas Fabienne, Gladieff Laurence, Toulas Christine
Oncogenetics Laboratory, Oncopole Claudius Regaud, IUCT-Oncopole, Toulouse, France.
DIAD, Inserm, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France.
Int J Mol Sci. 2023 Sep 20;24(18):14348. doi: 10.3390/ijms241814348.
Even though male breast cancer (MBC) risk encompasses both genetic and environmental aetiologies, the primary risk factor is a germline pathogenic variant (PV) or likely pathogenic variant (LPV) in and/or genes. To identify new potential MBC-specific predisposition genes, we sequenced a panel of 585 carcinogenesis genes in an MBC cohort without PV/LPV. We identified 14 genes carrying rare PVs/LPVs in the MBC population versus noncancer non-Finnish European men, predominantly coding for DNA repair and maintenance of genomic stability proteins. We identified for the first time PVs/LPVs in (pre-mRNA processing), (transcription regulation), and (maintenance of genomic stability) as well as in genes involved in other cellular processes. To study the specificity of this MBC PV/LPV profile, we examined whether variants in the same genes could be detected in a female breast cancer (FBC) cohort without PV/LPV. Only 5/109 women (4.6%) carried a PV/LPV versus 18/85 men (21.2%) on these genes. FBC did not carry any PV/LPV on 11 of these genes. Although 5.9% of the MBC cohort carried PVs/LPVs in and neither of these genes were altered in our FBC cohort. Our data suggest that in addition to , other genes involved in DNA repair/maintenance or genomic stability as well as cell adhesion may form a specific MBC PV/LPV signature.
尽管男性乳腺癌（MBC）的风险包括遗传和环境病因，但主要风险因素是BRCA1和/或BRCA2基因中的种系致病变异（PV）或可能的致病变异（LPV）。为了鉴定新的潜在MBC特异性易感基因，我们对一组585个致癌基因进行了测序，该组基因来自一个没有BRCA PV/LPV的MBC队列。我们在MBC人群与非癌症的非芬兰欧洲男性中鉴定出14个携带罕见PVs/LPVs的基因，这些基因主要编码DNA修复和基因组稳定性维持蛋白。我们首次在PRPF31（前体mRNA加工）、ZNF365（转录调控）、MCPH1（基因组稳定性维持）以及参与其他细胞过程的基因中鉴定出PVs/LPVs。为了研究这种MBC PV/LPV谱的特异性，我们检查了在一个没有BRCA PV/LPV的女性乳腺癌（FBC）队列中是否能检测到相同基因中的变异。在这些基因上，只有5/109名女性（4.6%）携带PV/LPV，而男性为18/85名（21.2%）。FBC在其中11个基因上没有携带任何PV/LPV。尽管MBC队列中有5.9%的人在ATM和PALB2中携带PVs/LPVs，但在我们的FBC队列中这两个基因都没有改变。我们的数据表明，除了BRCA1/2之外，其他参与DNA修复/维持或基因组稳定性以及细胞黏附的基因可能形成特定的MBC PV/LPV特征。
