Feasibility of neonatal dried blood spot retrieval amid evolving state policies (2009-2010): a Children's Oncology Group study

Dried blood spots (DBS) are collected uniformly from US newborns to test for metabolic and other disorders. Because evidence exists for prenatal origins of some diseases, DBS may provide unique prenatal exposure records. Some states retain residual DBS and permit their use in aetiological studies. The primary study aim was to assess the feasibility of obtaining residual DBS from state newborn screening programmes for paediatric and adolescent cancer patients nationwide with parental/subject consent/assent. Families of leukaemia and lymphoma patients aged ≤21 years diagnosed from 1998 to 2007 at randomly selected Children's Oncology Group institutions across the US were questioned (n = 947). Parents/guardians and patients aged ≥18 years were asked to release DBS to investigators in spring 2009. DBS were then requested from states. Overall, 299 families (32%) released DBS. Consenting/assenting patients were born in 39 US states and 46 DBS were obtained from five states; 124 DBS were unobtainable because patients were born prior to dates of state retention. State policies are rapidly evolving and there is ongoing discussion regarding DBS storage and secondary research uses. Currently, population-based DBS studies can be conducted in a limited number of states; fortunately, many have large populations to provide reasonably sized paediatric subject groups

The majority of total nuclear-encoded non-ribosomal RNA in a human cell is 'dark matter' un-annotated RNA

<p>Abstract</p> <p>Background</p> <p>Discovery that the transcriptional output of the human genome is far more complex than predicted by the current set of protein-coding annotations and that most RNAs produced do not appear to encode proteins has transformed our understanding of genome complexity and suggests new paradigms of genome regulation. However, the fraction of all cellular RNA whose function we do not understand and the fraction of the genome that is utilized to produce that RNA remain controversial. This is not simply a bookkeeping issue because the degree to which this un-annotated transcription is present has important implications with respect to its biologic function and to the general architecture of genome regulation. For example, efforts to elucidate how non-coding RNAs (ncRNAs) regulate genome function will be compromised if that class of RNAs is dismissed as simply 'transcriptional noise'.</p> <p>Results</p> <p>We show that the relative mass of RNA whose function and/or structure we do not understand (the so called 'dark matter' RNAs), as a proportion of all non-ribosomal, non-mitochondrial human RNA (mt-RNA), can be greater than that of protein-encoding transcripts. This observation is obscured in studies that focus only on polyA-selected RNA, a method that enriches for protein coding RNAs and at the same time discards the vast majority of RNA prior to analysis. We further show the presence of a large number of very long, abundantly-transcribed regions (100's of kb) in intergenic space and further show that expression of these regions is associated with neoplastic transformation. These overlap some regions found previously in normal human embryonic tissues and raises an interesting hypothesis as to the function of these ncRNAs in both early development and neoplastic transformation.</p> <p>Conclusions</p> <p>We conclude that 'dark matter' RNA can constitute the majority of non-ribosomal, non-mitochondrial-RNA and a significant fraction arises from numerous very long, intergenic transcribed regions that could be involved in neoplastic transformation.</p

Psychological Research in Childhood Cancer: The Children’s Oncology Group Perspective

Objective To review benefits and barriers to psychological research on childhood cancer in multidisciplinary, multicenter clinical-trial cooperative groups and identify opportunities for research activities in the coming decade. Methods Review of progress of cooperative-group research in the Children’s Oncology Group and legacy groups and the contribution of psychological research to this effort. Results Multidisciplinary, multicenter clinical-trial cooperative groups offer opportunities for psychological research that may be impossible at local institutions. Benefits include collaboration with other disciplines, access to adequate numbers of participants, shared research infrastructure, and access to longitudinal cohorts. Barriers include cost, standardization and quality control, competition for limited resources, and authorship and publication challenges. Conclusions The inclusion of psychological research as a task of the multidisciplinary cooperative group contributes to a transdisciplinary science focused on cure of childhood cancer followed by optimal quality of survivorship. The focus of this research for the next decade should be on the development of intervention studies that address acute problems, lessen the impact of late effects of treatment, and ultimately prevent these effects by better diagnostic classification and targeted treatment. This focus should ultimately lead to translation of intervention research findings to standard of care in the larger childhood cancer community

Medication Exposures and Subsequent Development of Ewing Sarcoma: A Review of FDA Adverse Event Reports

Background. Ewing sarcoma family of tumors (ESFT) are rare but deadly cancers of unknown etiology. Few risk factors have been identified. This study was undertaken to ascertain any possible association between exposure to therapeutic drugs and ESFT. Methods. This is a retrospective, descriptive study. A query of the FDA Adverse Event Reporting System (FAERS) was conducted for all reports of ESFT, January 1, 1998, through December 31, 2013. Report narratives were individually reviewed for patient characteristics, underlying conditions and drug exposures. Results. Over 16 years, 134 ESFT reports were identified, including 25 cases of ESFT following therapeutic drugs and biologics including immunosuppressive agents and hormones. Many cases were confounded by concomitant medications and other therapies. Conclusions. This study provides a closer look at medication use and underlying disorders in patients who later developed ESFT. While this study was not designed to demonstrate any clear causative association between ESFT and prior use of a single product or drug class, many drugs were used to treat immune-related disease and growth or hormonal disturbances. Further studies may be warranted to better understand possible immune or neuroendocrine abnormalities or exposure to specific classes of drugs that may predispose to the later development of ESFT