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Wilms tumor (WT) is the most common childhood kidney cancer worldwide and poses a cancer health disparity to black children of sub-Saharan African ancestry. Although overall survival from WT at 5 years exceeds 90% in developed countries, this pediatric cancer is alarmingly lethal in sub-Saharan Africa and specifically in Kenya (36% survival at 2 years). Although multiple barriers to adequate WT therapy contribute to this dismal outcome, we hypothesized that a uniquely aggressive and treatment-resistant biology compromises survival further. To explore the biologic composition of Kenyan WT (KWT), we completed a next generation sequencing analysis targeting 10 WT-associated genes and evaluated whole-genome copy number variation. The study cohort was comprised of 44 KWT patients and their specimens. Fourteen children are confirmed dead at 2 years and 11 remain lost to follow-up despite multiple tracing attempts. TP53 was mutated most commonly in 11 KWT specimens (25%), CTNNB1 in 10 (23%), MYCN in 8 (18%), AMER1 in 5 (11%), WT1 and TOP2A in 4 (9%), and IGF2 in 3 (7%). Loss of heterozygosity (LOH) at 17p, which covers TP53, was detected in 18% of specimens examined. Copy number gain at 1q, a poor prognostic indicator of WT biology in developed countries, was detected in 32% of KWT analyzed, and 89% of these children are deceased. Similarly, LOH at 11q was detected in 32% of KWT, and 80% of these patients are deceased. From this genomic analysis, KWT biology appears uniquely aggressive and treatment-resistant., (© 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.)

MicroRNAs are important negative regulators of protein-coding gene expression and have been studied intensively over the past years. Several measurement platforms have been developed to determine relative miRNA abundance in biological samples using different technologies such as small RNA sequencing, reverse transcription-quantitative PCR (RT-qPCR) and (microarray) hybridization. In this study, we systematically compared 12 commercially available platforms for analysis of microRNA expression. We measured an identical set of 20 standardized positive and negative control samples, including human universal reference RNA, human brain RNA and titrations thereof, human serum samples and synthetic spikes from microRNA family members with varying homology. We developed robust quality metrics to objectively assess platform performance in terms of reproducibility, sensitivity, accuracy, specificity and concordance of differential expression. The results indicate that each method has its strengths and weaknesses, which help to guide informed selection of a quantitative microRNA gene expression platform for particular study goals.

Background/aim: High-calcium diets modulate energy metabolism and suppress inflammatory stress. These effects are primarily mediated by calcium suppression of calcitriol. We have now investigated the effect of additional components in dairy products [branched-chain amino acids (BCAA) and angiotensin-converting enzyme inhibitors (ACEi)] on adipocyte and muscle metabolism in an animal model of diet-induced obesity., Methods: aP2-agouti mice were fed four different 70% restricted diets for 6 weeks: basal-restricted diet (0.4% Ca), nonfat dry milk (1.2% Ca), calcium-depleted milk (0.4% Ca), or basal-restricted diet (0.4% Ca) with supplemented BCAA/ACEi. A high-density oligonucleotide microarray approach was used to compare the effects on energy metabolism., Results: Lipogenic genes in adipose tissue were downregulated in the milk group while in muscle protein synthetic pathways were stimulated by the Ca-depleted and low Ca/BCAA/ACEi diets. Pathways involved in inflammation were altered in adipose tissue and muscle by all three diet treatment groups., Conclusions: The results support our previous findings that calcium and BCAA contribute to the alteration of energy partitioning between adipose tissue and muscle. They provide further evidence for a calcium-independent effect of BCAA and ACEi in energy metabolism and inflammation., (Copyright 2009 S. Karger AG, Basel.)