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1.  The ectopic expression of BRCA1 is associated with genesis, progression, and prognosis of breast cancer in young patients 
Diagnostic Pathology  2012;7:181.
Objective
The study is to explore the histopathological features and the molecular marker expression of young women with breast cancers.
Methods
The pathological data of 367 cases of female breast cancer patients were retrospectively analyzed, focusing on the analysis of young breast cancer incidence trends and the clinical and pathological features.
Results
Compared with elderly breast cancer patients, young women with breast cancers had larger tumor sizes, higher histological grades, and lymph node metastasis rates. The majority of patients were in the PTNM III stage, with the clinical and pathological features of strong invasiveness. The positive expression rate of the BRCA1 protein in the young group was higher than that in the old group. BRCA1 expression was positively correlated with the PTNM stage and axillary lymph node metastasis (P < 0.05).
Conclusions
The ectopic expression of BRCA1 is associated with the genesis, progression, and prognosis of young breast cancer patients.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1628000054838044
doi:10.1186/1746-1596-7-181
PMCID: PMC3541118  PMID: 23276146
BRCA1; WWOX; Gene detection
2.  The DNA Methylome of Human Peripheral Blood Mononuclear Cells 
PLoS Biology  2010;8(11):e1000533.
Analysis across the genome of patterns of DNA methylation reveals a rich landscape of allele-specific epigenetic modification and consequent effects on allele-specific gene expression.
DNA methylation plays an important role in biological processes in human health and disease. Recent technological advances allow unbiased whole-genome DNA methylation (methylome) analysis to be carried out on human cells. Using whole-genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per strand), we report a comprehensive (92.62%) methylome and analysis of the unique sequences in human peripheral blood mononuclear cells (PBMC) from the same Asian individual whose genome was deciphered in the YH project. PBMC constitute an important source for clinical blood tests world-wide. We found that 68.4% of CpG sites and <0.2% of non-CpG sites were methylated, demonstrating that non-CpG cytosine methylation is minor in human PBMC. Analysis of the PBMC methylome revealed a rich epigenomic landscape for 20 distinct genomic features, including regulatory, protein-coding, non-coding, RNA-coding, and repeat sequences. Integration of our methylome data with the YH genome sequence enabled a first comprehensive assessment of allele-specific methylation (ASM) between the two haploid methylomes of any individual and allowed the identification of 599 haploid differentially methylated regions (hDMRs) covering 287 genes. Of these, 76 genes had hDMRs within 2 kb of their transcriptional start sites of which >80% displayed allele-specific expression (ASE). These data demonstrate that ASM is a recurrent phenomenon and is highly correlated with ASE in human PBMCs. Together with recently reported similar studies, our study provides a comprehensive resource for future epigenomic research and confirms new sequencing technology as a paradigm for large-scale epigenomics studies.
Author Summary
Epigenetic modifications such as addition of methyl groups to cytosine in DNA play a role in regulating gene expression. To better understand these processes, knowledge of the methylation status of all cytosine bases in the genome (the methylome) is required. DNA methylation can differ between the two gene copies (alleles) in each cell. Such allele-specific methylation (ASM) can be due to parental origin of the alleles (imprinting), X chromosome inactivation in females, and other as yet unknown mechanisms. This may significantly alter the expression profile arising from different allele combinations in different individuals. Using advanced sequencing technology, we have determined the methylome of human peripheral blood mononuclear cells (PBMC). Importantly, the PBMC were obtained from the same male Han Chinese individual whose complete genome had previously been determined. This allowed us, for the first time, to study genome-wide differences in ASM. Our analysis shows that ASM in PBMC is higher than can be accounted for by regions known to undergo parent-of-origin imprinting and frequently (>80%) correlates with allele-specific expression (ASE) of the corresponding gene. In addition, our data reveal a rich landscape of epigenomic variation for 20 genomic features, including regulatory, coding, and non-coding sequences, and provide a valuable resource for future studies. Our work further establishes whole-genome sequencing as an efficient method for methylome analysis.
doi:10.1371/journal.pbio.1000533
PMCID: PMC2976721  PMID: 21085693
3.  Immunohistochemical analysis of Metadherin in proliferative and cancerous breast tissue 
Diagnostic Pathology  2010;5:38.
Background
Metadherin (MTDH) has been reported to be associated with cancer progression in various types of human cancers including breast cancer. Whether MTDH contributes to carcinogenesis of breast cancer is still unknown. In the present study, we investigated the expression of MTDH in normal, UDH (usual ductal hyperplasia), ADH (atypical ductal hyperplasia), DCIS (ductal carcinoma in situ) and invasive cancer to explore the possible role of MTDH for breast cancer carcinogenesis.
Methods
Immunohistochemistry was employed on paraffin sections of surgical removed breast samples.
Results
The immunohistochemical results showed almost no staining in normal tissue, moderate staining in ADH and UDH, intense MTDH stains in DCIS and cancer. Statistical analysis demonstrated significant different MTDH expression between proliferative and cancerous breast lesions (p < 0.001). MTDH was positively correlated with the histological differentiation of DCIS (p = 0.028). In breast cancer, statistical analysis revealed a significant correlation between MTDH expression with patients' age (p = 0.042), ER status (p = 0.018) and p53 status (p = 0.001). We also examined the effect of MTDH on cell proliferation in DCIS and cancer, and we found that MTDH overexpression was significantly correlated with high Ki67 index (p = 0.008 and p = 0.036, respectively).
Conclusions
MTDH overexpression could be identified in proliferative breast lesions and may contribute to breast cancer progression.
doi:10.1186/1746-1596-5-38
PMCID: PMC2906416  PMID: 20565850

Results 1-3 (3)