ABSTRACT: 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 infor- mation. 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 sub- group, 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 differ- ences 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 geno- mic subgroup so far defined in FBC. 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 infor- mation. 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 sub- group, 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 differ- ences 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 geno- mic subgroup so far defined in FBC. Tumor cellularity was determined on H&E-stained sections and only tumors with high tumor cell content were included. DNA was extracted from fresh frozen tissue using a modification of a back-extraction protocol from the organic phase of the Qiagen Lipid mini RNA kit (Qiagen, Valencia, CA) as follows: 1 M Tris-buffer containing 4 M Guanidine Thiocyanate and 50 mM Sodium Citrate, followed by glycogen precipitation. DNA quality was assessed with a BioAnalyzer. Sufficient good quality DNA from 56 fresh frozen MBC tumors was available for high-resolution tiling BAC aCGH. BAC arrays, containing about 32,000 BAC clones mapped to the UCSC Human Genome build 17, were produced at the SCIBLU Genomics Resource Center, Lund University, Sweden. The aCGH data were normalized using PopLowess. Circular binary segmentation (CBS) was used for breakpoint analysis with an a of 0.01 and segments containing at least four probes were used in subsequent analyses.
