[Tissue heterogeneity analysis of CGG-repeat mutation in two fragile X affected male fetuses].

OBJECTIVE: To compare the CGG-repeat-length and its methylation status in fetal tissues and to explicate the heterogeneity of CGG repeats. METHOD: Multiple tissues from a full mutation(August 2013) and a mosaic aborted fetus of 23-week gestation(May 2012) were collected and genomic DNA from these tissues was extracted. The CGG-repeat-length and methylation status in fetal tissues were determined by a combined strategy of Southern blotting and GC-Rich PCR. FMR1 expression was measured by real time PCR and Western blotting. RESULT: CGG-repeat-length in different tissues of each fetus was similar.A major methylated band in the full mutation range (540 CGG repeats) was detected in the brain, skin, testis and kidney tissues of Case 1. An unmethylated premutation band with 160 CGG repeats, and another two bands with 470 and 1 100 CGG repeats in the full mutation range were shown in the brain, skin, testis, lung, stomach, gut, liver, kidney, heart and blood of Case 2. However, the methylation status of CGG repeats in the mosaic fetus was heterogeneous among different tissues. The lowest premutation ratio was in the brain of the mosaic fetus compared with other tissues, and correspondingly FMR1 expression in its brain was minimum. CONCLUSION: This study clarify the tissue heterogeneity of CGG repeats and provides information for the genetic counseling and clinical diagnosis in fragile X syndrome. Based on the fact that the mosaic fetus' mother is a carrier of full mutation, it is speculated that the maternal CGG repeat has contracted before the differentiation of trilaminar germ disc.

miR-125a-5p expression is associated with the age of breast cancer patients.

Dysregulated miR-125 observed in multiple cancer types has suggested that it is involved in malignant proliferation and invasion. However, the clinical significance of miR-125 in human breast cancer (BC) has not yet been fully elucidated. In the present study, the expression of miR-125a-5p/3p and miR-125b in 143 pairs of BC and normal adjacent tissues (NATs) was measured by real-time quantitative PCR, and the correlation between expression and clinicopathological features was explored. miR-125a-5p and miR-125b were significantly down-regulated in BC tissue samples compared with their matched NAT samples, while the difference in miR-125a-3p expression between BC tissues and NATs was not statistically significant. The expression level of miR-125a-5p was found to be significantly higher in younger patients (<35 years) than in older patients (≥35, P = 0.005). When the patients were divided into three groups according to age (<35, 36-48, and ≥48 years), a gradual reduction in miR-125a-5p expression was observed in BC tissue samples that correlated to increases in age (P = 0.009). There were no significant correlations between miR-125 expression and other clinicopathological features including tumor size, histological grade, hormone receptor status, Her-2 status, and lymph node metastasis. Taken together, these findings suggest that miR-125a-5p may play an important role in BC progression in an age-dependent manner, and that the down-regulation of miR-125a-5p and miR-125b may serve as independent predictors for breast cancer.

Effects of soy isoflavone and endogenous oestrogen on breast cancer in MMTV-erbB2 transgenic mice.

OBJECTIVE: Soy isoflavone is associated with modification of breast cancer risk. Effects of dietary isoflavone on breast tissue carcinogenesis under varying endogenous oestrogen contexts were investigated. METHODS: Five-week-old mouse mammary tumour virus (MMTV)-erbB2 female transgenic mice (n = 180) were divided into three equal groups: low-, normal- and high-oestrogen groups. Each group was then subdivided into an experimental group (given soybean feed) and a control group (given control feed). RESULTS: In the high-oestrogen environment, breast cancer incidence was significantly lower in the experimental versus the control group, whereas in the low-oestrogen environment, breast cancer incidence was significantly higher in the experimental versus the control group. There were no between-group differences in mean breast tumour latency, mean largest tumour diameter and breast tumour tissue vascular endothelial growth factor levels. CONCLUSIONS: Dietary soy isoflavones promote breast cancer at low oestrogen levels but inhibit breast cancer at high oestrogen levels. This effect may only occur during the initiation stage of breast cancer.