Integrating genomics to dig deeper into Wilms tumour biology

A new study provides a comprehensive catalogue of the genetic changes in Wilms tumour. Understanding the interplay between genetic and epigenetic aberrations during tumorigenesis and clonal evolution is fundamental to enabling prediction of who is at risk and which tumours will relapse when so many are curable

Estimation of introgression in cutthroat trout populations using microsatellites

Introgressive hybridization, mediated by anthropogenic activity, poses a threat to numerous and diverse taxa. The management of introgressed individuals or populations within species of conservation concern is currently the subject of scientific and political debate. We investigate the utility of 10 non-diagnostic microsatellite loci for investigating admixture from introduced Yellowstone cutthroat trout (Oncorhynchus clarkii bouvieri) and rainbow trout (O. mykiss) within 25 putative Rio Grande cutthroat trout (O. c. virginalis) populations. We apply five different approaches (correspondence analysis, maximum-likelihood assignment tests, an admixture estimator based on allele frequencies, an admixture estimator based on coalescent theory and an admixture estimator implementing a Bayesian method) and use two alternative O. c. virginalis reference samples. All approaches were capable of identifying one population that consisted entirely of introduced O. c. bouvieri, and three out of five approaches enabled us to discriminate those populations with relatively high levels of non-native introgression from those populations with little or none. Actual estimates of admixture coefficients within a test population, varied, however, with the approach and reference sample used. These results have important implications for policies dividing populations into different management categories according to the estimated proportion of non-native genetic material that they contain

Genetic diversity within fragmented cutthroat trout populations

Interior cutthroat trout Oncorhynchus clarkii have undergone severe declines over the past 150 years. Many subspecies now persist in a highly fragmented state, primarily within headwater streams. We used 12 microsatellites to investigate the population genetic characteristics of 22 remnant populations of Rio Grande cutthroat trout O. c. virginalis isolated in montane streams in New Mexico. Populations varied markedly in the amount of genetic diversity they contained. There was no significant relationship between estimated adult population size or habitat size and heterozygosity; however, populations occurring above natural barriers were significantly less diverse. Seven population samples exhibited significant deviations from Hardy-Weinberg equilibrium. Interlocus variance in the population inbreeding coefficient F-1S was correlated with habitat size, and several population samples exhibited a significantly higher variance in interindividual relatedness, or a significantly higher median individual inbreeding coefficient. than would be expected by chance. These results suggest that cutthroat trout populations in headwater streams consist of multiple partially discrete subpopulations in which only a small number of adults successfully reproduce. The potential for Such population substructure should be considered when planning management activities for stream-dwelling cutthroat trout

Wilms tumor: "State-of-the-art" update, 2016

Despite an impressive increase in survival rate over the past decades, there is still a need to improve the survival of specific subgroups of Wilms tumor (anaplastic, metastatic, and bilateral) and to decrease the late effects of treatment in terms of renal function and heart toxicity. We aim to explore new areas of improvement, from diagnosis to treatment: in the field of radiology the increased use of MRI and exploration of its diffusion-weighted imaging capabilities to predict WT histology at diagnosis and for preoperative assessment; in biology the emergence of new biomarkers that could be integrated into the decision-making process; and surgical techniques with more accurate indication of nephron-sparing surgery that is no longer reserved for bilateral WT and the minimally invasive approach. The long-term outcome of patients with WT should thus be a strong indicator of the improvement in adapting and personalizing the treatment to each individual

Role of CD56 in Normal Kidney Development and Wilms Tumorigenesis

The cell-surface glycoprotein CD56 has three major isoforms that play important roles in cell adhesion and signaling, which may promote cell proliferation, differentiation, survival, or migration. It is an important molecule in normal kidney development and acts as a key marker in Wilms tumor stem and progenitor cells. Here, we review the structural and genetic features of the CD56 glycoprotein, and summarize its roles in the normal versus diseased metanephric blastema. We discuss areas of CD56-related research that may complement or improve existing Wilms tumor treatment strategies, including the antibody-drug conjugate lorvotuzumab mertansine that binds to CD56

Bilateral Wilms tumour: a review of clinical and molecular features

Wilms tumour (WT) is the most common paediatric kidney cancer and affects approximately one in 10 000 children. The tumour is associated with undifferentiated embryonic lesions called nephrogenic rests (NRs) or, when diffuse, nephroblastomatosis. WT or NRs can occur in both kidneys, termed bilateral disease, found in only 5–8% of cases. Management of bilateral WT presents a major clinical challenge in terms of maximising survival, preserving renal function and understanding underlying genetic risk. In this review, we compile clinical data from 545 published cases of bilateral WT and discuss recent progress in understanding the molecular basis of bilateral WT and its associated precursor NRs in the context of the latest radiological, surgical and epidemiological features

Evidence for a delay in diagnosis of Wilms' tumour in the UK compared with Germany: implications for primary care for children

The UK has a longstanding system of general practice which provides the vast majority of primary care, including that for children. It acts as a 'gatekeeper' to more specialist care. Parents may also use accident and emergency departments as their first point of medical contact for their children. Outcomes in the UK for many conditions in children appear to be worse than in comparable European countries where there is direct access to care by paediatricians. We have therefore looked at pathways to diagnosis and compared outcomes in the childhood kidney cancer, Wilms' tumour, which has been treated in the UK and Germany within the same clinical trial for over a decade. We find that Wilms' tumours are significantly larger in volume and have a more advanced tumour stage at diagnosis in the UK compared to Germany. There is a small (∼3%) difference in event free and overall survival between the two countries. Our data suggest that the system of primary care for children in the UK is less likely to result in the incidental finding of an abdominal mass in a child with no or vague symptoms. This may be a reason for the poorer outcome

Population structure and genetic management of Rio Grande cutthroat trout (Oncorhynchus clarkii virginalis)

The Rio Grande cutthroat trout, Oncorhynchus clarkii virginalis, has declined precipitously over the past century, and currently exhibits a highly fragmented distribution within the Canadian, Pecos and Rio Grande river systems of the western United States. The relationships between populations in the three river drainages, and between O. c. virginalis and the closely related taxa O. c. pleuriticus and O. c. stomias, are not well understood. In order to guide management decisions for the subspecies, we investigated the distribution of variation at 12 micro-satellite loci and two regions of the mitochondrial genome. We observed a high level of genetic differentiation between O. c. virginalis populations occupying different headwater streams ( global F-st = 0.41). However, we found evidence for previous gene flow within the Rio Grande drainage, indicating that inter-population differentiation may have been exacerbated by the recent effects of population fragmentation. Despite large-scale anthropogenic movement of individuals from the Rio Grande into the Canadian and Pecos, the genetic signature of long-term evolutionary independence between the three drainages has been retained

Incidence of childhood renal tumours: An international population-based study

Malignant renal tumours represent 5% of childhood cancers and include types with likely different aetiology: Wilms tumour (WT), rhabdoid renal tumour, kidney sarcomas and renal carcinomas. WT is the most common renal tumour in children, previously shown to vary internationally and with ethnicity. Using the comprehensive database of the International Incidence of Childhood Cancer study (IICC), we analysed global variations and time trends in incidence of renal tumour types in children (age 0‐14 years) and adolescents (age 15‐19 years). The results were presented by 14 world regions, and five ethnic groups in the United States. We included 15 320 renal tumours in children and 800 in adolescents reported to the 163 contributing registries during 2001‐2010. In children, age‐standardised incidence rate (ASR) of renal tumours was 8.3 per million (95% confidence interval, CI = 8.1, 8.4); it was the highest in North America and Europe (9‐10 per million) and the lowest in most Asian regions (4‐5 per million). In the United States, Blacks had the highest ASR (10.9 per million, 95% CI = 10.2, 11.6) and Asian and Pacific Islanders the lowest (4.4 per million, 95% CI = 3.6, 5.1). In adolescents, age‐specific incidence rate of renal tumours was 1.4 per million (95% CI = 1.3, 1.5). WT accounted for over 90% of all renal tumours in each age from 1 to 7 years and the proportion of renal carcinomas increased gradually with age. From 1996 to 2010, incidence remained mostly stable for WT (average annual percent change, AAPC = 0.1) and increased for renal carcinomas in children (AAPC = 3.7) and adolescents (AAPC = 3.2). Our findings warrant further monitoring