High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer
High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer
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DOI：
10.1007/s10549-010-1262-8
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发表时间：
2011-10-01
影响因子：
3.8
通讯作者：
Hedenfalk, Ingrid
中科院分区：
文献类型：
--
作者：
Johansson, Ida;Nilsson, Cecilia;Hedenfalk, Ingrid
男性乳腺癌（MBC）非常罕见，在分子水平上的特征很少。利用高分辨率基因组数据，我们旨在通过基因组失衡来表征MBC，并将其与女性乳腺癌（FBC）进行比较，并进一步研究基因组谱是否具有任何预后信息。采用高分辨率平铺BAC阵列对56例新鲜冷冻MBC肿瘤进行分析。使用癌症显著靶点基因组鉴定（GISTIC）分析评估病例之间的共同显著区域。359例FBC肿瘤的公开基因组数据集用于参考目的。数据显示了广泛的畸变模式，证实了MBC是一种异质性肿瘤类型。基因组增加在MBC中比在FBC中更常见，通常涉及整个染色体臂，而基因组物质的损失较少。最常见的畸变在两性之间相似，但高水平的扩增在FBC中更为常见。我们在MBCs中确定了两个基因组亚群；男性情结和男性单纯。男性复合体亚组与先前报道的光复合体FBC亚组表现出惊人的相似性，而男性单纯性亚组似乎代表了仅发生在男性中的乳腺癌的新亚组。在基因组失衡方面，FBC和MBC有许多相似之处，但高分辨率基因组分析也揭示了明显的差异。MBC可分为两个全面的基因组亚群，这可能具有预后价值。男性单一亚群与迄今为止在FBC中定义的任何基因组亚群明显不同。
Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic information. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays. Significant regions in common between cases were assessed using Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. A publicly available genomic data set of 359 FBC tumors was used for reference purposes. The data revealed a broad pattern of aberrations, confirming that MBC is a heterogeneous tumor type. Genomic gains were more common in MBC than in FBC and often involved whole chromosome arms, while losses of genomic material were less frequent. The most common aberrations were similar between the genders, but high-level amplifications were more common in FBC. We identified two genomic subgroups among MBCs; male-complex and male-simple. The male-complex subgroup displayed striking similarities with the previously reported luminal-complex FBC subgroup, while the male-simple subgroup seems to represent a new subgroup of breast cancer occurring only in men. There are many similarities between FBC and MBC with respect to genomic imbalances, but there are also distinct differences as revealed by high-resolution genomic profiling. MBC can be divided into two comprehensive genomic subgroups, which may be of prognostic value. The male-simple subgroup appears notably different from any genomic subgroup so far defined in FBC.