Background:Yolk sac tumours (YSTs) and germinomas are the two major pure histological subtypes of germ cell tumours. To date, the role of DNA methylation in the aetiology of this class of tumour has only been analysed in adult testicular forms and with respect to only a few genes.Methods:A bank of paediatric tumours was analysed for global methylation of LINE-1 repeat elements and global methylation of regulatory elements using GoldenGate methylation arrays.Results:Both germinomas and YSTs exhibited significant global hypomethylation of LINE-1 elements. However, in germinomas, methylation of gene regulatory regions differed little from control samples, whereas YSTs exhibited increased methylation at a large proportion of the loci tested, showing a ‘methylator' phenotype, including silencing of genes associated with Caspase-8-dependent apoptosis. Furthermore, we found that the methylator phenotype of YSTs was coincident with higher levels of expression of the DNA methyltransferase, DNA (cytosine-5)-methyltransferase 3B, suggesting a mechanism underlying the phenotype.Conclusion:Epigenetic silencing of a large number of potential tumour suppressor genes in YSTs might explain why they exhibit a more aggressive natural history than germinomas and silencing of genes associated with Caspase-8-dependent cell death might explain the relative resistance of YSTs to conventional therapy.

Three-dimensional chromatin organization varies across cell types and is essential for gene regulation. However, current technologies are unable to assess in vivo genome-wide chromatin organization non-invasively. Here we show that distant correlations in the fragment length of cell-free DNA (cfDNA) recapitulate three-dimensional chromatin organization. The inferred organization is highly concordant with that measured by Hi-C in white blood cells from healthy donors, and is not explained by technical bias or sequence composition. Furthermore, the inferred organization reflects different genomic organization in the various cell types contributing to cfDNA, allowing identification and quantification of tissues of origin. This approach is concordant with previous methods, but with more complete representations of cfDNA. Our results, demonstrated in cfDNA from healthy individuals and cancer patients, may enable noninvasive monitoring of in vivo genome organization and accurate quantification of cell death in different clinical conditions.

Introduction: Complementary and alternative medicine (CAM) is garnering increasing interest and acceptance among the general population. Although usage is thought to be widespread among paediatric cancer patients, local studies have not been done. We aimed to investigate the prevalence and predictors of CAM usage in paediatric cancer patients in a single institution. Materials and Methods: Parents of 73 paediatric cancer patients treated at KK Women’s & Children’s Hospital completed an interviewer-administered questionnaire. Data about the types of CAM therapies used, motivations for use, adverse effects, costs and discussion of usage with the patient’s physician were obtained. General perceptions towards CAM and conventional medicine were explored. A subsequent telephone survey enquired about spirituality, benefits of CAM use and overall satisfaction with the therapies. Results: Two-thirds of patients used at least 1 CAM treatment, mainly as supportive adjuncts to conventional cancer treatment. Dietary changes, health supplements, herbal tea and bird’s nest were the most common therapies used. Few patients (8.1%) consulted a CAM practitioner. Positive predictors of CAM usage included being of Chinese race, the practice of Buddhism or Taoism, the use of CAM prior to diagnosis, perception of CAM effectiveness and dissatisfaction with conventional treatment. Significantly, 55.1% of the parents had not discussed their CAM usage with their child’s physician. Conclusions: A substantial proportion of paediatric cancer patients utilises CAM therapies, often without their physician’s knowledge. Healthcare providers need to remain cognisant of the potential implications of CAM usage in order to proactively counsel patients. This would ensure that conventional therapy remains uncompromised.