Alpha satellite is a tandemly organized type of repetitive DNA that comprises 5% of the genome and is found at all human centromeres. A defined number of 171-bp monomers are organized into chromosome-specific higher-order repeats (HORs) that are reiterated thousands of times. At least half of all human chromosomes have two or more distinct HOR alpha satellite arrays within their centromere regions. We previously showed that the two alpha satellite arrays of Homo sapiens Chromosome 17 (HSA17), D17Z1 and D17Z1-B, behave as centromeric epialleles, that is, the centromere, defined by chromatin containing the centromeric histone variant CENPA and recruitment of other centromere proteins, can form at either D17Z1 or D17Z1-B. Some individuals in the human population are functional heterozygotes in that D17Z1 is the active centromere on one homolog and D17Z1-B is active on the other. In this study, we aimed to understand the molecular basis for how centromere location is determined on HSA17. Specifically, we focused on D17Z1 genomic variation as a driver of epiallele formation. We found that D17Z1 arrays that are predominantly composed of HOR size and sequence variants were functionally less competent. They either recruited decreased amounts of the centromere-specific histone variant CENPA and the HSA17 was mitotically unstable, or alternatively, the centromere was assembled at D17Z1-B and the HSA17 was stable. Our study demonstrates that genomic variation within highly repetitive, noncoding DNA of human centromere regions has a pronounced impact on genome stability and basic chromosomal function.

Ovarian cancer is the eighth-most common cause of death among women worldwide. In the absence of distinctive symptoms in the early stages, the majority of women are diagnosed in advanced stages of the disease. Surgical debulking and systemic adjuvant chemotherapy remain the mainstays of treatment, with the development of chemoresistance in up to 75% of patients with subsequent poor treatment response and reduced survival. Therefore, there is a critical need to revisit existing, and identify potential biomarkers that could lead to the development of novel and more effective predictors for ovarian cancer diagnosis and prognosis. The capacity of these biomarkers to predict the existence, stages, and associated therapeutic efficacy of ovarian cancer would enable improvements in the early diagnosis and survival of ovarian cancer patients. This review not only highlights current evidence-based ovarian-cancer-specific prognostic and diagnostic biomarkers but also provides an update on various technologies and methods currently used to identify novel biomarkers of ovarian cancer.

No abstract

Genomic variation is a source of functional diversity that is typically studied in genic and non-coding regulatory regions. However, the extent of variation within noncoding portions of the human genome, particularly highly repetitive regions, and the functional consequences are not well understood. Satellite DNA, including α satellite DNA found at human centromeres, comprises up to 10% of the genome, but is difficult to study because its repetitive nature hinders contiguous sequence assemblies. We recently described variation within α satellite DNA that affects centromere function. On human chromosome 17 (HSA17), we showed that size and sequence polymorphisms within primary array D17Z1 are associated with chromosome aneuploidy and defective centromere architecture. However, HSA17 can counteract this instability by assembling the centromere at a second, "backup" array lacking variation. Here, we discuss our findings in a broader context of human centromere assembly, and highlight areas of future study to uncover links between genomic and epigenetic features of human centromeres.

Background: To evaluate the knowledge, perception and attitudes towards human papilloma virus (HPV) among pre-university students in Malaysia. Study design : In this cross sectional study, between November 2013 to March 2014, in a public university, a convenient sampling method was used. A total of 716 respondents were recruited and interviewed with a set of standard questionnaires for assessment of knowledge, perception and attitudes towards HPV and predictor variables associated with level of knowledge. Results: Almost half (48.9%) of the respondents scored less than 5 and were categorised as having poor knowledge. Three hundred and twelve (43.6%) respondents had moderate knowledge and only 54 (7.5%) respondents exhibited good knowledge with the score of 11 and above. Only 142 (20%) students perceived themselves to be vulnerable to HPV infection though 560 (78.2%) students thought that HPV infection is a serious disease. Perceived benefits and desire to be vaccinated were significantly associated with gender (p=0.000) and knowledge of HPV vaccine and cervical cancer (p=0.000). Conclusions: The level of knowledge regarding HPV among the pre-university students was low. However, student intention for vaccination increased with increasing level of knowledge. Thus, efforts to improve knowledge and awareness should be prioritised to increase uptake of the HPV vaccination programme and hence reduce morbidity and mortality from consequences of HPV infection, including cervical carcinoma.

No abstract

Endometrial cancer (EC) is one of the most common malignancies of the female genital tract and its current treatment mainly relies on surgical removal of the tumour bulk, followed by adjuvant radiotherapy with or without chemotherapy/hormonal therapy. However, the outcomes of these approaches are often unsatisfactory and are associated with severe toxicity and a higher recurrence rate of the disease. Thus, more clinical research exploring novel medical intervention is needed. Involvement of the immune pathway in cancer has become important and the finding of a high positive expression of programmed cell death-ligand 1 (PD-L1) in EC may offer a better targeted therapeutic approach. Numerous studies on the PD-L1 role in EC have been conducted, but the results remained inconclusive. Hence, this systematic review was conducted to provide an update and robust analysis in order to determine the pooled prevalence of PD-L1 expression in EC and evaluate its association with clinicopathological features in different focuses of tumour cells (TC) and immune cells (IC). A comprehensive literature search was conducted using the PubMed, Web of Science, and Scopus databases. Twelve articles between 2016 and 2021 with 3023 EC cases met the inclusion criteria. The effect of PD-L1 expression on the outcome parameters was estimated by the odds ratios (ORs) with 95% confidence intervals (CIs) for each study. The pooled prevalence of PD-L1 was 34.26% and 51.39% in the tumour cell and immune cell, respectively, among women with EC. The PD-L1 expression was significantly associated with Stage III/IV disease (in both TC and IC) and correlated to the presence of lympho-vascular invasion in IC. However, the PD-L1 expression in TC was not associated with the age groups, histology types, myometrial invasion, and lympho-vascular invasion. In IC, PD-L1 expression was not associated with age group, histology type, and myometrial invasion. The meta-analysis survival outcomes of PD-L1 high expression had a significant association with worse OS in IC but not in TC.

Objective This study aims to describe the menstrual pattern and menstrual care of girls with intellectual disabilities and to evaluate the impact of menstruation and awareness of parents/guardians on girls with intellectual disabilities. Methodology Parents/guardians of girls aged 9–17 years with known intellectual disabilities who attended a scheduled public forum and Paediatrics and Adolescent Gynaecology Clinic (PAC) were recruited in a questionnaire-based study. Results A total of 123 parents/guardians with a mean age of 41.83 ± 5.45 years completed the questionnaire. The mean age of girls with intellectual disabilities was 12.28 ± 2.78 years, and the mean menarcheal age was 11.12 ± 1.76 years. Only 53 (43.1%) parents/guardians were aware of availability of menstrual suppression. Parents/guardians with lower family income (OR = 0.00; 95% CI = 0.00–0.20), unable to manage menses (OR = 0.03; 95% CI = 0.00–0.61), and moderate severity of menses (OR = 0.01; 95% CI = 0.00–1.21), were associated with seeking medical help on menstrual suppression. The factors associated with parents/guardians requesting for sterilization were lower family income (OR = 0.02; 95% CI = 0.00–0.36) and concern about sexual abuse (OR = 0.25; 95% CI = 0.06–0.39). Conclusion Menstrual pattern in girls with intellectual disabilities is similar to those without disabilities. Parents/guardians' knowledge and awareness on menstrual suppression were still lacking.