Cases Of Wilms Tumor Research Articles

Abstract 261: Long-read sequencing characterization of a patient with bilateral Wilms tumor of unknown etiology

Abstract Wilms tumor is the most common childhood kidney cancer. 15% of patients with Wilms tumor have germline pathogenic variants in genes or regions such as WT1 or the 11p15 region. Variants in these regions can include structural or copy number alterations or alterations in methylation. In the majority of cases of Wilms tumor no known pathogenic variant could be found using the state-of-the-art technologies, including comprehensive approaches such as Illumina whole exome sequencing. One explanation for this is that such technologies have difficulties in detecting structural variants (SVs) in areas associated with repeat or low complexity sequence. In addition, Illumina technology does not immediately support direct methylation detection. Therefore, we hypothesized that analysis of bilateral Wilms tumor of unknown etiology using long-read sequencing could reveal molecular events of potential clinical interest. We performed in-depth genomic analysis on a whole blood DNA sample from a patient with a bilateral Wilms tumor. This patient had no significant family history of cancer, and previously tested negative for Beckwith-Wiedemann syndrome by methylation testing of the 11p15 region; clinical exome sequencing of the patient's germline detected no variants associated with Wilms tumors. We sequenced the genome at 40x depth using PromethION Nanopore sequencing. 29180 SVs (deletions or insertions larger than 30 base pairs) were detected using Sniffles and 26480 were detected with SVIM. Only SVs that were detected by both methods were considered for downstream analysis. Variants were annotated and filtered using a short-read catalog of SVs (gnomAD-SV), a long-read catalog, the Database of Genomic Variants catalog, and by comparison to 11 in-house genomes. We focused on SVs, copy number variants, and methylation events affecting genes previously associated with Wilms tumor. Our long-read sequencing approach detected compound heterozygotes using phased variant calls. A heterozygous missense mutation was identified in haplotype one, while a 300 base pair insertion in an ALU element was present in haplotype two. These two compound heterozygous variants overlap an exon of the OVCH2 gene, and the ALU element was not detected by the prior Illumina analysis. Additionally, we determined the frequency of methylation in CpG sites genomewide using nanopolish. Using a normal blood sample from an unrelated individual as a control, we searched for extreme differences across large and gene promoter regions. Hypermethylation in the promoter regions of genes in the 11p15.5 locus was observed in the patient as compared to the control. Hypomethylation in this region is associated with Beckwith-Wiedemann syndrome. In conclusion, nanopore technology is able to detect variants missed by Illumina sequencing, and has the potential to yield new findings of interest in a case of a child with suspected cancer predisposition syndrome. Citation Format: Allison R. Cheney, Jean Monlong, Holly C. Beale, Hugh Olsen, Ellen Towle Kephart, Katrina Learned, Shanna White, Julian A. Martinez-Agosto, Noah Federman, Mark Akeson, Miten Jain, Vivian Y. Chang, Olena M. Vaske. Long-read sequencing characterization of a patient with bilateral Wilms tumor of unknown etiology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 261.

Expression of PAX2 and PAX8 in Wilms Tumor: A Tissue Microarray-based Immunohistochemical Study.

Background & Objective:There is currently inadequate information about the expression of immunohistochemical markers in pediatric tumors. Paired box genes 2 and 8 (PAX2 and PAX8) genes have an essential role in kidney organogenesis. This study aimed to investigate the IHC expression of PAX2 and PAX8 in Wilms tumor. Such study would be helpful in diagnosis and possibly in differentiation of this tumor from other mimics, especially in those of poorly differentiated type in small needle biopsy specimens.Methods:We performed a cross-sectional study on 45 Wilms tumor cases referred to Bahrami pediatric hospital between 2005 and 2015. Demographic data were collected from medical documents. Sections from related paraffin blocks were provided by the tissue microarray method, and immunohistochemical (IHC) staining was done for PAX8 and PAX2.Results:The mean tumor size was 9.98±4.95 cm. Favorable histology was seen in 84.4% of samples. PAX2 was expressed in 41 cases (91.1%), and PAX8 in 37 patients (82.2%). PAX2 and PAX8 expression was mostly seen in both blastemal and epithelial components (77.8% and 66.6%), respectively. Tumors with favorable and unfavorable histology did not significantly differ in PAX2 and PAX8 expression (P=0.637). We found a statically significant relationship between PAX8 expression and tumor size (P=0.033). Conclusion:PAX2 and PAX8 markers might helpful in diagnosis of Wilms tumor and may differentiate it from other histologically similar kidney tumors. PAX8 expression may be associated with larger tumor size. Tumors with favorable and unfavorable histology may not be different in PAX2 and PAX8 expression.

Impact of YTHDF1 gene polymorphisms on Wilms tumor susceptibility: A five-center case-control study.

BackgroundWilms tumor is the most frequent renal malignancy in children. YTHDF1 is associated with the development of several kinds of cancers, yet whether common variants of the YTHDF1 gene influence Wilms tumor risk is unknown. We present, here, a hospital‐based case‐control study specifically designed to investigate the role of YTHDF1 genetic variants on Wilms tumor.MethodsWe successfully genotyped samples of 408 Wilms tumor cases and 1198 controls which were collected from five hospitals across China. The unconditional logistic regression was adopted to analyze the contributions of YTHDF1 gene single nucleotide polymorphisms (SNPs) to the risk of Wilms tumor. The odds ratio (OR) and 95% confidence interval (CI) were generated to evaluate the conferring risk of YTHDF1 gene SNPs (rs6011668 C>T, rs6090311 A>G).ResultsNeither of the two SNPs could contribute to the risk of Wilms tumor. A negative association was also detected in the combined effects of protective genotypes on Wilms tumor risk. The stratification analysis revealed that compared with those with CC genotype, rs6011668 CT/TT genotype was associated with increased Wilms tumor risk in those ≤18 months (OR = 1.54, 95% CI = 1.02–2.30, p = 0.038), and with decreased Wilms tumor risk in those >18 months (OR = 0.70, 95% CI = 0.50–0.97, p = 0.034).ConclusionOur present work sheds some light on the potential role of YTHDF1 gene polymorphisms on Wilms tumor risk.

A rare case of Wilms Tumor in the right atrium.

Improvement in outcome of Malignant solid tumor cases is credited to existence of well-defined guidelines and protocols and integrated treatment modalities involving chemotherapy, surgery and radiotherapy. The present case describes a rare case of Wilms tumor extending from the left kidney to left renal vein and then via inferior vena cava into the right atrium. This patients was 5 years of age and resident of Karachi presented to the outdoor of National Institute of Child Health (NICH) with the complaints of progressively increasing abdominal distension over the last two months that exacerbated with the agony of swelling in both lower limbs. On physical examination, a mass was palpable in the left abdominal area not crossing the midline. On initial scrutiny with haematological testing and the basic radiology workup in the form of ultrasound abdomen, the patient was found to have a mass originating in the left kidney and invading the left renal vein. CT scan abdomen with contrast revealed that the patient had a heterogeneously enhancing mass of 12 X 9 cm originating from the left kidney and invading the left renal vein. The size of the tumor encroaching into the right atrium cavity was 19.5 X 20.5 mm.

CT in the prize in charge of wilms 'tumor (monocentric study of 13 cases)

Nephroblastoma or Wilms tumor is a malignant tumor that develops at the expense of embryonic kidney tissue. It is the most common kidney tumor in children (> 90%); it represents around 5% to 14% of all childhood cancers. The aim of our work is to recall the contribution of imaging, in particular CT, in the management of this renal tumor. This is a retrospective, single-center study of 136 cases of Wilms tumors diagnosed in our clinic over a 2-year period. The mean age of the patients was 04 years with an extreme of (3 months -12 years) with a female prevalence (8 girls for 5 boys). Abdominal mass dominated in our study in clinical information. Histological confirmation was found in 12 cases, the only non-conforming case was lost to follow-up.

Role of expression of p53 and Ki67 in the progression of Wilms tumor; correlation with survival

Background: Wilms tumor (WT) is the most frequent renal tumor of childhood and is a highly responsive tumor to chemotherapy. P53 and ki67 are two of the most important markers that have been evaluated in many cancers. The role of p53 in the pathogenesis and progression of WT is only partly understood. Over the past decade, the importance of Ki-67 in the prognosis of breast cancer has been widely studied. On the other hand, fewer studies are available for this in WT. Aim: To study the possible role of p53 and ki67 in the progression and outcome of Wilms tumor cases. Methods: Immunohistochemical (IHC) staining for p53 and ki67 were done and correlated with clinicopathological data of Wilms tumor cases. Results: There was a positive correlation between p53 and ki67 expression and unfavorable histology, higher tumor stage, shorter disease-free survival (DFS) and overall survival (OS). Conclusion: Ki67 and p53 expression was positively correlated with aggressive behavior of Wilms tumor

The following 3 cases were presented at the 2020 virtual PUOWG conferenceLate Presentation of Wilms Tumor in a Patient with Hemihypertrophy after Normal Screening

An identifiable genetic malformation or predisposition syndrome is present in 18% of Wilms tumor cases. Given this, children with conditions associated with a greater than 1% risk of developing Wilms tumor are recommended to have regular surveillance imaging with renal ultrasound until age 7. Seven years is the recommended screening duration because 95% of cases will occur by this age. We present a case of a child with isolated hemihypertrophy, associated with 5% risk of Wilms tumor, who presented with a tumor after the recommended screening, at age 9, brining into question the age cutoffs currently used.

A Case of Wilms Tumor with a Tumor Thrombus in a Boy with WAGR Syndrome

A Case of Wilms Tumor with a Tumor Thrombus in a Boy with WAGR Syndrome

Penetrance of WT1 and WT2 Gene Mutation and Loss of Heterozygosity in Wilms tumors in Indian Population

Wilms tumor is a nephroblastoma of pediatric age group and heterogeneous in nature. WT1 and WT2 gene mutations are involved in onset of tumorigenesis in syndromic and non syndromic cases of Wilms tumor. Present study has been designed with aim to evaluate the frequency of WT1 and WT2 gene mutation, loss of heterozygosity (LOH) and DNA copy number variation (CNV) in clinically diagnosed cases of Wilms tumor using RT-PCR based analysis. Findings reveals that there was vast difference in the mutation frequency between WT1 (7.5%) and WT2 (17.5) gene, and statistical analysis shows significant difference (p < 0.05) in WT2 mutation and calculated value of C.I. varies between 0.886-1.990 at 95% with odd ratio (7.52). Interestingly, the frequency of LOH (loss of heterozygosity and DNA copy number variations (CNVs) shows significant difference (p < 0.01), suggesting increase of genetic susceptibility and penetrance of gene in proband of the family tumor resulting increase of risk factor after using three different microsatellite DNA markers (DS11S935, DS11S904 and DS11S1363). Genetic heterogenecity were also observed by calculating Tm values, between cases and controls (GAPDH), and C.I. varies between 0.292 - 2.270 at 95% with O.R = 0.54 in D11S1363 and maximum value of C.I. was 1.165-2.165 at 95% with O.R = 0.50 in D11S1905 and the p = 0.194 & p = 0.522 respectively, between cases and controls..

Adult Wilms Tumour Cases Masquerading as Renal Cell Carcinoma

Adult Wilms Tumour Cases Masquerading as Renal Cell Carcinoma

Application of the pathological classification of "CCCG-WT-2016" (2019 revision) for treatment of Wilms tumors

Objective: To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors. Methods: Ninety-one cases of Wilms tumor diagnosed at Shanghai Children's Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016." Results: The specimens were obtained by core biopsy (n=21), primary nephrectomy (n=41), post-chemotherapy nephrectomy/resection (n=18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) (n=11). The specimens of core biopsy and primary nephrectomy (n=62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk (n=0), intermediate risk (n=10) and high risk (n=2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk (n=0), intermediate risk (n=5) and high risk (n=1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions: The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.

ALKBH5 gene polymorphisms and Wilms tumor risk in Chinese children: A five-center case-control study.

BackgroundWilms tumor is a frequently diagnosed renal cancer among children with unclear genetic causes. N6‐methyladenosine (m6A) modification genes play critical roles in tumorigenesis. However, whether genetic variations of m6A modification genes predispose to Wilms tumor remain unclear. ALKBH5 (AlkB homolog 5), a crucial member of m6A modification genes, encodes a demethylase that functions to reverse m6A RNA methylation.MethodsHerein, we evaluated the association of single nucleotide polymorphisms (SNPs) in the m6A modification gene ALKBH5 and Wilms tumor susceptibility in a large multi‐center case‐control study. A total of 414 Wilms tumor cases and 1199 healthy controls were genotyped for ALKBH5 rs1378602 and rs8400 polymorphisms by TaqMan.ResultsNo significant association was detected between these two polymorphisms and Wilms tumor risk. Moreover, 1, 2, and 1‐2 protective genotypes (rs1378602 AG/AA or rs8400 GG) did not significantly reduce Wilms tumor risk, compared with risk genotypes only. Stratification analysis revealed a significant relationship between rs1378602 AG/AA genotypes and decreased Wilms tumor risk in children in clinical stage I diseases [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.32‐0.98, P = .042]. The presence of 1‐2 protective genotypes was correlated with decreased Wilms tumor risk in subgroups of age > 18 months, when compared to the absence of protective genotypes (adjusted OR = 0.74, 95% CI = 0.56‐0.98, P = .035).ConclusionCollectively, our results demonstrate that ALKBH5 SNPs may exert a weak influence on susceptibility to Wilms tumor. This finding increases the understanding of the role of the m6A gene in tumorigenesis of Wilms tumor.

RNA-Sequencing, Connectivity Mapping, and Molecular Docking to Investigate Ligand-Protein Binding for Potential Drug Candidates for the Treatment of Wilms Tumor.

BackgroundWilms tumor, or nephroblastoma, is a malignant pediatric embryonal renal tumor that has a poor prognosis. This study aimed to use bioinformatics data, RNA-sequencing, connectivity mapping, molecular docking, and ligand-protein binding to identify potential targets for drug therapy in Wilms tumor.Material/MethodsWilms tumor and non-tumor samples were obtained from high throughput gene expression databases, and differentially expressed genes (DEGs) were analyzed using the voom method in the limma package. The overlapping DEGs were obtained from the intersecting drug target genes using the Connectivity Map (CMap) database, and systemsDock was used for molecular docking. Gene databases were searched for gene expression profiles for complementary analysis, analysis of clinical significance, and prognosis analysis to refine the study.ResultsFrom 177 cases of Wilms tumor, there were 648 upregulated genes and 342 down-regulated genes. Gene Ontology (GO) enrichment analysis showed that the identified DEGs that affected the cell cycle. After obtaining 21 candidate drugs, there were seven overlapping genes with 75 drug target genes and DEGs. Molecular docking results showed that relatively high scores were obtained when retinoic acid and the cyclin-dependent kinase inhibitor, alsterpaullone, were docked to the overlapping genes. There were significant standardized mean differences for three overlapping genes, CDK2, MAP4K4, and CRABP2. However, four upregulated overlapping genes, CDK2, MAP4K4, CRABP2, and SIRT1 had no prognostic significance.ConclusionsRNA-sequencing, connectivity mapping, and molecular docking to investigate ligand-protein binding identified retinoic acid and alsterpaullone as potential drug candidates for the treatment of Wilms tumor.

Association between genetic variations in LIN28/let-7 pathway and Wilms tumor susceptibility

To investigate the correlation between genetic variants of key genes in LIN28/let-7 pathway and the risk of Wilms tumor in Chinese population. We performed a four-centre hospital-based case-control study including 355 Wilms tumor cases and 1070 controls with the purpose to determine whether the potentially functional single nucleotide polymorphisms in LIN28/let-7 pathway core genes are associated with Wilms tumor risk in Chinese children. DNA was extracted and genotyping was performed using TaqMan assays. Genotype frequencies of the polymorphisms and the demographic variables between Wilms tumor cases and controls were compared using the chi-squared test. The associations between the selected polymorphisms and Wilms tumor risk were measured by calculating the odds ratios (ORs) and 95% confidence intervals (CIs), using unconditional univariate and multivariate logistic regression analyses. Stratified analysis was used to identify the association between genotypes in subgroups and the risk of Wilms tumor. 1.LIN28A rs3811463 T>C and rs34787247 G>A were associated with increased risk of Wilms tumor.2.LIN28B rs314276 C>A was associated with decreased risk of Wilms tumor.3.Individuals harboring KRAS rs12587 GT genotype were more likely to develop Wilms tumor than those carrying the GG genotype.4.No associations with risk of Wilms tumor were found for the selected SNPs of the HMGA2 gene.5.No associations with risk of Wilms tumor were found for the selected SNPs of the CYMC gene. The LIN28A rs3811463 T>C and rs34787247 G>A, LIN28B rs314276 C>A and KRAS rs12587 G>T may contribute to risk of Wilms tumor in Chinese population. More centres, larger, prospective studies with different ethnic populations are warranted to validate our findings.

Diagnostic Utility of BCOR Antibody in Clear Cell Sarcomas of Kidney.

Purpose. Clear cell sarcoma of the kidney (CCSK) is an uncommon malignant renal tumor. It is the second most common renal pediatric renal malignancy after Wilms tumor. It exhibits a heterogeneous morphology, with overlapping features with its close differentials, which results in diagnostic challenges. There was no specific immunohistochemical marker in the past, to help in this regard. BCOR antibody has recently been suggested to be helpful in the differential diagnosis. We aim to study the utility of the BCOR antibody in the diagnosis of CCSK. Methods. We selected a total of 27 cases of CCSK (n = 12), Wilms tumor (n = 12), and congenital mesoblastic nephroma (n = 3). All cases were evaluated for the extent and intensity of nuclear labeling for BCOR antibody by immunohistochemistry (IHC). Results. We found that BCOR IHC was positive in 11 out of 12 cases with diffuse and strong staining in 8 of the cases. None of the cases of Wilms tumor and congenital mesoblastic nephroma were positive. Only 2 cases of Wilms tumor showed minimal and weak staining in <5% of cells. Conclusion. Diffuse and strong nuclear staining for the BCOR antibody is highly specific for CCSK among common pediatric renal malignancies. Our study confirms that BCOR IHC is a good IHC marker for the diagnosis of CCSK.

Origins of DNA methylation defects in Wilms tumors.

Wilms tumor is an embryonic renal cancer that typically presents in early childhood and accounts for 7% of all paediatric cancers. Different genetic alterations have been described in this malignancy, however, only a few of them are associated with a majority of Wilms tumors. Alterations in DNA methylation, in contrast, are frequent molecular defects observed in most cases of Wilms tumors. How these epimutations are established in this tumor is not yet completely clear. The recent identification of the molecular actors required for the epigenetic reprogramming during embryogenesis suggests novel possible mechanisms responsible for the DNA methylation defects in Wilms tumor. Here, we provide an overview of the DNA methylation alterations observed in this malignancy and discuss the distinct molecular mechanisms by which these epimutations can arise.

Comparison of 3-Dimensional and Augmented Reality Kidney Models With Conventional Imaging Data in the Preoperative Assessment of Children With Wilms Tumors

Nephron-sparing surgery can be considered in well-defined cases of unilateral and bilateral Wilms tumors, but the surgical procedure can be very challenging for the pediatric surgeon to perform. To assess the added value of personalized 3-dimensional (3-D) kidney models derived from conventional imaging data to enhance preoperative surgical planning. In a survey study, the conventional imaging data of 10 Dutch children with Wilms tumors were converted to 3-D prints and augmented reality (AR) holograms and a panel of pediatric oncology surgeons (n = 7) assessed the quality of the different imaging methods during preoperative evaluation. Kidney models were created with 3-D printing and AR using a mixed reality headset for visualization. Differences in the assessment of 4 anatomical structures (tumor, arteries, veins, and urinary collecting structures) using questionnaires. A Likert scale measured differences between the imaging methods, with scores ranging from 1 (completely disagree) to 5 (completely agree). Of the 10 patients, 7 were girls, and the mean (SD) age was 3.7 (1.7) years. Compared with conventional imaging, the 3-D print and the AR hologram models were evaluated by the surgeons to be superior for all anatomical structures: tumor (median scores for conventional imaging, 4.07; interquartile range [IQR], 3.62-4.15 vs 3-D print, 4.67; IQR, 4.14-4.71; P = .008 and AR hologram, 4.71; IQR, 4.26-4.75; P = .002); arteries (conventional imaging, 3.62; IQR, 3.43-3.93 vs 3-D print, 4.54; IQR, 4.32-4.71; P = .002 and AR hologram, 4.83; IQR, 4.64-4.86; P < .001), veins (conventional imaging, 3.46; IQR 3.39-3.62 vs 3-D print, 4.50; IQR, 4.39-4.68; P < .001 and AR hologram, 4.83; IQR, 4.71-4.86; P < .001), and urinary collecting structures (conventional imaging, 2.76; IQR, 2.42-3.00 vs 3-D print, 3.86; IQR, 3.64-4.39; P < .001 and AR hologram, 4.00; IQR, 3.93-4.58; P < .001). There were no differences in anatomical assessment between the two 3-D techniques (the 3-D print and AR hologram). In this study, the 3-D kidney models were associated with improved anatomical understanding among the surgeons and can be helpful in future preoperative planning of nephron-sparing surgery for Wilms tumors. These models may be considered as a supplementary visualization in clinical care.

Identification of new Wilms tumour predisposition genes: an exome sequencing study

SummaryBackgroundWilms tumour is the most common childhood renal cancer and is genetically heterogeneous. While several Wilms tumour predisposition genes have been identified, there is strong evidence that further predisposition genes are likely to exist. Our study aim was to identify new predisposition genes for Wilms tumour.MethodsIn this exome sequencing study, we analysed lymphocyte DNA from 890 individuals with Wilms tumour, including 91 affected individuals from 49 familial Wilms tumour pedigrees. We used the protein-truncating variant prioritisation method to prioritise potential disease-associated genes for further assessment. We evaluated new predisposition genes in exome sequencing data that we generated in 334 individuals with 27 other childhood cancers and in exome data from The Cancer Genome Atlas obtained from 7632 individuals with 28 adult cancers.FindingsWe identified constitutional cancer-predisposing mutations in 33 individuals with childhood cancer. The three identified genes with the strongest signal in the protein-truncating variant prioritisation analyses were TRIM28, FBXW7, and NYNRIN. 21 of 33 individuals had a mutation in TRIM28; there was a strong parent-of-origin effect, with all ten inherited mutations being maternally transmitted (p=0·00098). We also found a strong association with the rare epithelial subtype of Wilms tumour, with 14 of 16 tumours being epithelial or epithelial predominant. There were no TRIM28 mutations in individuals with other childhood or adult cancers. We identified truncating FBXW7 mutations in four individuals with Wilms tumour and a de-novo non-synonymous FBXW7 mutation in a child with a rhabdoid tumour. Biallelic truncating mutations in NYNRIN were identified in three individuals with Wilms tumour, which is highly unlikely to have occurred by chance (p<0·0001). Finally, we identified two de-novo KDM3B mutations, supporting the role of KDM3B as a childhood cancer predisposition gene.InterpretationThe four new Wilms tumour predisposition genes identified—TRIM28, FBXW7, NYNRIN, and KDM3B—are involved in diverse biological processes and, together with the other 17 known Wilms tumour predisposition genes, account for about 10% of Wilms tumour cases. The overlap between these 21 constitutionally mutated predisposition genes and 20 genes somatically mutated in Wilms tumour is limited, consisting of only four genes. We recommend that all individuals with Wilms tumour should be offered genetic testing and particularly, those with epithelial Wilms tumour should be offered TRIM28 genetic testing. Only a third of the familial Wilms tumour clusters we analysed were attributable to known genes, indicating that further Wilms tumour predisposition factors await discovery.FundingWellcome Trust.

Association of KRAS and NRAS gene polymorphisms with Wilms tumor risk: a four-center case-control study.

Wilms tumor is a type of pediatric solid tumor that arises partly due to somatic and germline mutations. Single-nucleotide polymorphisms (SNPs) in the RAS gene reportedly modify the risk for several types of human malignancies. We conducted a multicenter study to investigate whether RAS gene variants predispose individuals to Wilms tumor. Four SNPs in RAS were genotyped in 355 Wilms tumor cases and 1070 controls. The SNPs included rs12587 G>T, rs7973450 A>G and rs7312175 G>A in KRAS, and rs2273267 A>T in NRAS. Individuals harboring the rs12587 GT genotype were more likely to develop Wilms tumor than those carrying the GG genotype (adjusted odds ratio [OR]=1.30, 95% confidence interval [CI]=1.004-1.68, P=0.046). However, the other three SNPs seemed not to influence the risk for Wilms tumor. Compared to individuals without a risk genotype, those harboring one to three KRAS risk genotypes had an adjusted OR of 1.28 for developing Wilms tumor (95% CI=1.002-1.64, P=0.048). Stratification analysis revealed that rs12587 GT/TT was associated with Wilms tumor risk in children >18 months old (adjusted OR=1.39, 95% CI=1.02-1.89, P=0.037). Our findings indicate that the rs12587 G>T polymorphism in KRAS is associated with increased Wilms tumor susceptibility.

Expression of cyclin D1 in clear cell sarcoma of kidney. Is it useful in differentiating it from its histological mimics?

BackgroundClear cell sarcoma of the kidney (CCSK) is a rare malignant pediatric renal neoplasm with a heterogeneous histological appearance which often results in misdiagnosis. There are no specific immunohistochemical markers which can help in differentiating CCSK from other pediatric renal neoplasms. Recently Cyclin D1 has been investigated as a possible marker in this regard. In this study, we aim to determine the usefulness of Cyclin D1 in differentiating between CCSK and other pediatric renal neoplasms and to compare our results with those of recently published studies.MethodsA total of 48 cases of CCSK, Wilms tumor (WT), renal rhabdoid tumor, mesoblastic nephroma, renal Ewing sarcoma and neuroblastoma were included in the study. All cases were stained with cyclin D1. Extent of Cyclin D1 staining was graded according to percentage of positive tumor cells as diffuse (> 70%), focal (5 to 70%), and negative (< 5%). Intensity of Cyclin D1 staining was graded as strong or 3+, moderate or 2+ and weak or 1 + .ResultsMost or all cases of CCSK, neuroblastoma and renal Ewing sarcoma demonstrated diffuse and strong positivity for Cyclin D1. Most cases of Wilms tumor (epithelial component) also demonstrated diffuse and often strong positivity for Cyclin D1. In most cases of WT, blastemal component was negative.ConclusionsCyclin D1 is a sensitive but not specific immunohistochemical marker for CCSK and many other pediatric renal malignant neoplasms as well as for neuroblastoma. Hence, careful examination of histological features is important in reaching an accurate diagnosis in CCSKs. However, Cyclin D1 is very helpful in distinguishing between blastema-rich WT and CCSK.