Complete genome sequences of identical zika virus isolates in a nursing mother and her infant

CITATION: Blohm, G. M., et al. 2017. Complete genome sequences of identical zika virus isolates in a nursing mother and her infant. Genome Announcements, 5(17):1-2, doi:10.1128/genomeA.00231-17.The original publication is available at https://mra.asm.orgENGLISH ABSTRACT: Complete genome sequences were obtained for Zika viruses isolated from the breast milk of a Venezuelan patient and her child, who was exclusively breastfeeding at the time. These sequences are the first to be reported from a presumptive autochthonous postnatal transmission case from mother to child in Venezuela.https://mra.asm.org/content/5/17/e00231-17Publisher's versio

Morphologically Normal-Appearing Mammary Epithelial Cells Obtained from High-Risk Women Exhibit Methylation Silencing of INK4a/ARF.

Purpose: p16(INK4a) has been appreciated as a key regulator of cell cycle progression and senescence. Cultured human mammary epithelial cells that lack p16(INK4a) activity have been shown to exhibit premalignant phenotypes, such as telomeric dysfunction, centrosomal dysfunction, a sustained stress response, and, most recently, a dysregulation of chromatin remodeling and DNA methylation. These data suggest that cells that lack p16(INK4a) activity would be at high risk for breast cancer development and may exhibit an increased frequency of DNA methylation events in early cancer.Experimental Design: To test this hypothesis, the frequencies of INK4a/ARF promoter hypermethylation, as well as four additional selected loci, were tested in the initial random periareolar fine needle aspiration samples from 86 asymptomatic women at high risk for development of breast cancer, stratified using the Masood cytology index.Results: INK4a/ARF promoter hypermethylation was observed throughout all early stages of intraepithelial neoplasia and, importantly, in morphologically normal-appearing mammary epithelial cells; 29 of 86 subjects showed INK4a/ARF promoter hype rmethylation in at least one breast. Importantly, INK4a/ARF promoter hype rmethylation was not associated with atypia, and the frequency of hypermethylation did not increase with increasing Masood cytology score. The frequency of INK4a/ARF promoter hypermethylation was associated with the combined frequency of promoter hypermethylation of retinoic acid receptor-beta 2, estrogen receptor-alpha, and breast cancer-associated 1 genes (P = 0.001).Conclusions: Because INK4a/ARF promoter hype rmethylati on does not increase with age but increases with the frequency of other methylation events, we predict that INK4a/ARF promoter hypermethylation may serve as a marker of global methylation dysregulation.</p

Androgen Receptor Status Is A Prognostic Marker In Non-Basal Triple Negative Breast Cancers And Determines Novel Therapeutic Options

Triple negative breast cancers are a heterogeneous group of tumors characterized by poor patient survival and lack of targeted therapeutics. Androgen receptor has been associated with triple negative breast cancer pathogenesis, but its role in the different subtypes has not been clearly defined. We examined androgen receptor protein expression by immunohistochemical analysis in 678 breast cancers, including 396 triple negative cancers. Fifty matched lymph node metastases were also examined. Association of expression status with clinical (race, survival) and pathological (basal, non-basal subtype, stage, grade) features was also evaluated. In 160 triple negative breast cancers, mRNA microarray expression profiling was performed, and differences according to androgen receptor status were analyzed. In triple negative cancers the percentage of androgen receptor positive cases was lower (24.8% vs 81.6% of non-triple negative cases), especially in African American women (16.7% vs 25.5% of cancers of white women). No significant difference in androgen receptor expression was observed in primary tumors vs matched metastatic lesions. Positive androgen receptor immunoreactivity was inversely correlated with tumor grade (p<0.01) and associated with better overall patient survival (p = 0.032) in the non-basal triple negative cancer group. In the microarray study, expression of three genes (HER4, TNFSF10, CDK6) showed significant deregulation in association with androgen receptor status; eg CDK6, a novel therapeutic target in triple negative cancers, showed significantly higher expression level in androgen receptor negative cases (p<0.01). These findings confirm the prognostic impact of androgen receptor expression in non-basal triple negative breast cancers, and suggest targeting of new androgen receptor-related molecular pathways in patients with these cancers.PubMedWoSScopu