Project description: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.
Project description: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.
Project description:In this experiment, formalin-fixed paraffin-embedded male (n=15) and female (n=10) primary invasive ductal carcinoma (all ERα-positive, HER2-negative, node-negative) samples were selected and hybridized using the Almac Diagnostics Breast Cancer DSA(TM) array ADXBRCv2a520413 in order to investigate the gene expression differences between male and female breast cancer.
Project description:Characterization of DNA imbalances in a set of 25 MBC samples analyzed by high resolution CGH arrays in order to detect DNA copy number aberrations (CNAs). These results have been then compared with a female breast cancer dataset deposited with the Gene Expression Omnibus. Male patients affected by breast cancer have been consecutively selected for this retrospective study: 15 received the primary diagnosis of breast cancer at the NCC of Bari, while 10 at Regina Elena Institute of Rome, Italy. This dataset was compared to GSE12659 (female breast cancer).
Project description:This study demonstrates sex differences in the hormonal and immune landscape of the MMTV-PyMT transgenic murine model of female and male ER+ breast cancer using single-cell RNA sequencing
Project description:Before the onset of sexual differentiation, male and female external genitalia are morphologically indistinguishable. After the onset of sex-specific production of sex steroids by the gonads, the male and female external genitalia differentiate into either a penis or clitoris. Here we use single cell sequencing to investigate the similarities and differences of cell populations in the external genitalia during the critical sexual differentiation window in the mouse embryo. We found the male and female genitalia are largely similar in cell composition and gene expression at the bipotential stage of development. As sexual differentiation ensues, sex steroid-dependent and -independent differences in cell populations arise, leading to dimorphic establishment of the external genitalia.
Project description:Simple Markov model.
There are 3 disease states: Healthy, Sick, and Dead, where the Dead state is terminal.
The yearly transition probabilities are:
Healthy to Dead: 0.01; Healthy to Sick: 0.2 for Male and 0.1 for Female; Sick to Healthy: 0.1; Sick to Dead: 0.3.
The transition probability now depends on the cohort (Male or Female) and can be expressed as a function of a Boolean covariate Male.
Initial conditions: Healthy = (50 Male, 50 Female), Sick = (0,0) and Dead = (0,0).
Output: Number of men and women in each disease state for years 1-10.
Project description:Using 2 male and 2 female zebrafish (pool of 6) brain samples, we generated base-resolution DNA methylation maps to document sex-specific epigenetic differences.
Project description:Blastocyst-derived embryonic stem cells (ESCs) and gonad-derived embryonic germ cells (EGCs) represent two classic types of pluripotent cell lines, yet their molecular equivalence remains incompletely understood. Here, we compare genome-wide methylation patterns between isogenic ESC and EGC lines to define epigenetic similarities and differences. Surprisingly, we find that sex rather than cell type drives methylation patterns in ESCs and EGCs. Cell fusion experiments further reveal that the ratio of X chromosomes to autosomes dictates methylation levels, with female hybrids being hypomethylated and male hybrids being hypermethylated. We show that the X-linked MAPK phosphatase DUSP9 is upregulated in female compared to male ESCs, and its heterozygous loss in female ESCs leads to male-like methylation levels. However, male and female blastocysts are similarly hypomethylated, indicating that sex-specific methylation differences arise in culture. Collectively, our data demonstrate the epigenetic similarity of sex-matched ESCs and EGCs and identify DUSP9 as a regulator of female-specific hypomethylation.
Project description:Blastocyst-derived embryonic stem cells (ESCs) and gonad-derived embryonic germ cells (EGCs) represent two classic types of pluripotent cell lines, yet their molecular equivalence remains incompletely understood. Here, we compare genome-wide methylation patterns between isogenic ESC and EGC lines to define epigenetic similarities and differences. Surprisingly, we find that sex rather than cell type drives methylation patterns in ESCs and EGCs. Cell fusion experiments further reveal that the ratio of X-chromosomes to autosomes dictates methylation levels, with female hybrids being hypomethylated and male hybrids being hypermethylated. We show that the X-linked MAPK phosphatase DUSP9 is upregulated in female compared to male ESCs, and its heterozygous loss in female ESCs leads to male-like methylation levels. Notably, male and female blastocysts are similarly hypomethylated, indicating that sex-specific methylation differences arise in culture. Collectively, our data demonstrate the epigenetic similarity of sex-matched ESCs and EGCs and identify DUSP9 as a regulator of female-specific hypomethylation.