Loss of heterozygosity for chromosomes 16q in Wilms tumors predicts outcomes:A meta-analysis

BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.

Long range physical map of the Wilms' tumor-aniridia region on human chromosome 11

The relationship between genetic alterations at chromosomal band 11p13 and the WAGR(Wilms'tumor,aniridia,genitourinary anomalies,and mental retardation)syndrome is not clearly understood.To aid our understanding of this relationship,we have constructed a physical map of this region of the genome using pulsed field gel electrophoresis.Fifteen newly identified 11p13-specific probes and four previously reported probes were used to subdivide 11p13 into five intervals defined by overlapping constitutional deletions from several WAGR patients.This new repertoire of DNA probes was used to construct a physical map of this region using the infrequently cutting restriction enzymes MIuI and NotI.This map spans approximately 13 Mb and encompasses deletion and translocation breakpoints associated with genitourinary abnormalities,aniridia,and Wilms'tumor.The map also makes it possible to localize the genes for Wilms'tumor(WT)and aniridia(AN2)to a small number of specific NotI restriction fragments.

Detection of biomarkers in children with Wilms＇ tumor using proteinchip technology

Wilms＇ tumor is the most common pediatric tumor of the kidney. The most important factor affecting long term survival of this malignancy is recurrence after surgery. Early diagnosis, treatment and regular follow-up are critical to prevent recurrence and improve long-term survival rate. Currently,

Graft-versus-leukemia effects of Wilms＇ tumor 1 protein-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation

Background The role of Wilms＇ tumor 1 protein （WT1）-specific cytotoxic T cells （CTL） in eradicating chronic myeloid leukemia （CML） cells is to be established. The aim of this study was to determine whether WT1 contributed to the graft-versus-leukemia effects （GVLE） for CML following allogeneic hematopoietic stem cell transplantation （HSCT）. Methods High-resolution human leukocyte antigen （HLA） class I genotyping was performed by sequence-specific polymerase chain reaction （PCR）. Fifteen HLA-A~＊2402 patients with CML who underwent allogeneic HSCT were enrolled in this study. We monitored the frequency of WT1-specific CTL by pentamer assay and the molecular minimal residual disease by real-time quantitative PCR.Results A CD8＋ T-cell response to WT1 was observed in 14 of 15 patients after HSCT. The median frequencies of WT1-CTL were 0.54%, 0.62%, 0.81% and 1.28% （%CD8） on days 30, 60, 90 and 180, respectively. The median frequency of WT1-CTL （1.38%） in patients with molecular remission （MoR） was significantly higher than that in those without MoR （0.38%） on day 30, while no significant differences between them were detected on days 60, 90 and 180. The increase of WT1-CTL was associated with a decrease in bcr-abl expression and MoR; and the decrease of WT1-CTL was associated with an increase in bcr-abl expression, suggesting a WT1 -driven GVL effect. WT1-CTL had a predominant effector-memory phenotype （CD45RO＋CD27-CD57＋）.Conclusions The emergence of WT1-CTL with an effector-memory phenotype is associated with GVLE in CML patients after HSCT. This will pave the way for the WT1 vaccines to enhance GVLE after HSCT in CML.

Fine needle aspiration cytology of Wilms' tumor:a case report

Wilms' tumor is extremely rare.In this article,we reported one case diagnosed by fine needle aspiration cytology(FNAC) and pathology.A three and a half-year-old boy was admitted to hospital with abdominal pain for two days.CT scan showed a large mass in the region of the left kidney of the boy.FNAC was performed on the mass,and the cytologic specimen showed malignant cells suggestive of a Wilms' tumor.Histologic examination of the operative specimen after the left nephrectomy also revealed Wilms' tumor.

Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用

目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。

基于高通量RNA测序分析Wilms瘤中关键基因对预后及免疫应答的影响

目的探索肾母细胞瘤(WT)中关键基因及其对预后和免疫应答的潜在影响。方法采用高通量RNA测序技术分析临床肿瘤样本和配对正常组织的mRNA全面表达谱,并鉴定差异表达基因。使用GO、KEGG和GSEA富集分析探索差异表达基因在肾母细胞瘤中的潜在生物学功能和机制。使用STRING数据库鉴定HUB基因。LASSO回归用于构建HUB基因预后模型。基于cBioPortal平台分析关键HUB基因的突变特征并对其免疫治疗效果进行预测。采用qPCR验证关键HUB基因的差异表达。结果本研究筛选出1612个差异表达基因,其中1030个上调,582个下调。GO、KEGG或GSEA富集分析显示,差异基因集与细胞周期和免疫应答有关,一定程度上参与了WT的发生发展。基于STRING数据库构建差异基因的PPI网络,进一步确定了10个HUB基因。其中4个HUB基因(TP53、MED1、CCNB1和EGF)被证实与WT患儿的生存密切相关。通过LASSO回归分析构建WT患者的三基因预后签名,根据该签名将患者分为高危或低危组,生存分析显示显著的预后差异(HR=1.814,Log-rank P=0.002)。该模型的3年、5年和7年生存ROC曲线的AUC值均大于0.7。突变分析显示,关键HUB基因整体突变或TP53/CCNB1的单独突变与较低的生存率密切相关,其中TP53高表达与较差的免疫治疗疗效有关。qPCR结果显示,关键HUB基因在肿瘤组织和细胞中呈现出显著的表达差异。结论TP53基因在WT中发挥重要作用,可能成为新的免疫治疗生物标志物和治疗靶点。

Identification and analysis of mutations in WTX and WT1 genes in peripheral blood and tumor tissue of children with Wilms＇ tumor

Background Wilms＇ tumor （nephroblastoma） is the most common pediatric kidney cancer. Only one Wilms＇ tumor gene is known, WT1 at 11p13, which is mutated in 5%-10% of Wilms＇ tumors. Recently, mutations were reported in WTX at Xq11.1 in Wilms＇ tumors. This study investigated the mutation proportion, type, and distribution in WTX and WT1 in children with Wilms＇ tumor. The role of WTX/WT1 in the development of Wilms＇ tumor, and the relationship between clinical phenotype and genotype, were also studied. Methods Wilms＇ tumor specimens （blood samples from 70 patients and tumor tissue samples from 52 patients） were used. A long fragment of WTXand 10 exons and intron sequences of WT1 were amplified by polymerase chain reaction （PCR） from extracted genomic DNA and sequenced. A chi-square test compared the difference between the W-/-X mutation group and the no mutation group. The relationship between the mutations and clinical phenotype was analyzed. Results W7X mutations were found in 5/52 tumor tissues and in 2/70 peripheral blood samples （five cases in total, all point mutations）. Two patients had a WTX mutation in both samples. WT1 mutations were found in 2/52 tumor tissues and in 4/70 peripheral blood samples （five cases in total, all point mutations）. One patient had a WT1 mutation in both samples. Ten cases had WTX or WT1 mutation （19.2% of Wilms＇ tumors）. No overlapping WTX and WTI mutations were found. No significant differences in clinical parameters were found between patients with and without a W7X mutation. Conclusions WTX mutations occur early in Wilms＇ tumor development, but at a low proportion. There was no evidence that WTX is the main cause of Wilms＇ tumor. Clinical parameters of patients with WTX mutations are not related to the mutation, indicating a limited impact of WTX on tumor progression. WTX and WT1 mutations occur independently, suggesting a relationship between their gene products.

Extrarenal Wilms’ Tumor of the Female Genital System:A Case Report and Literature Review

Extrarenal Wilms’ Tumors (ERWTs) are rare. There have been only 25 cases of ERWT arising from the female genital system reported in the literature. In this paper, we report a 60-year-old woman with a complaint of vaginal bleeding and a polypoid mass in the uterine cavity by sonography that was demonstrated as ERWT by pathology after resection. The pathological characteristics, histological origination,diagnosis, therapy and prognosis of ERWT in female reproductive system are discussed in this paper in the purpose of improving the diagnosis and therapy of this rare tumor.

Prognostic Factors of Wilms＇ Tumor Complicated with Nephroblastomatosis

Nephrogenic rests （NRs） are abnormally persistent clusters of embryonal cells, representing microscopic dysplasias of the developing kidney. NRs are found in approximately 1% of infant kidneys at autopsy. Nephroblastomatosis signifies the presence of multiple or diffuse NRs. Both NRs and nephroblastomatosis were known as precursor lesions of Wilms tumor,Nephroblastomatosis can be classified into four categories： Perilobar （PEN R only）; i ntralobar （I LNR only）; combined （PLNR and ILNR）; and universal. The diagnosis and treatment of Wilms＂ tumor have been improved constantly and achieved common sense. However, little information is available regarding Wilms＂ tumor associated with nephroblastomatosis for lower prevalence. This study aimed to investigate the prognostic factors of Wilms＇ tumor associated with nephroblastomatosis.

Spontaneous xenogeneic GvHD in Wilms'tumor Patient-Derived xenograft models and potential solutions

Severely immunocompromised NOD.Cg-PrkdcIl2rg(NOG)mice are among the ideal animal recipients for generation of human cancer models.Transplantation of human solid tumors having abundant tumor-i nfiltrating lymphocytes(TILs)can induce xenogeneic graft-versus-host disease(xGvHD)following engraftment and expansion of the TILs inside the animal body.Wilms’tumor(WT)has not been recognized as a lymphocyte-predominant tumor.However,3 consecutive generations of NOG mice bearing WT patient-derived xenografts(PDX)xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention.In the initial generation,dermatitis,auto-amputation of digits,weight loss,lymphadenopathy,hepatitis,and interstitial pneumonitis were observed.Despite antibiotic treatment,no response was noticed,and thus the animals were prematurely euthanized(day 47 posttransplantation).Laboratory and histopathologic evaluations revealed lymphoid infiltrates positively immunostained with anti-human CD3 and CD8 antibodies in the xenografts and primary tumor,whereas no microbial infection or lymphoproliferative disorder was found.Mice of the next generation that lived longer(91 days)developed sclerotic skin changes and more severe pneumonitis.Cutaneous symptoms were milder in the last generation.The xenografts of the last 2 generations also contained TILs,and lacked lymphoproliferative transformation.The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD.While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts,this report for the first time documented serial xGvHD in consecutive passages of WT PDX-bearing models and discussed potential solutions to prevent such an undesired complication.

Wilms tumor with dilated cardiomyopathy: A case report

BACKGROUND Wilms tumor is the most common renal malignancy in childhood. It occurs primarily between the ages of 2 and 5 years. The usual manifestations are abdominal mass, hypertension, and hematuria. The case presented here had an unusual presentation, with dilated cardiomyopathy and hypertension secondary to the Wilms tumor. CASE SUMMARY A 3-year-old boy presented with a 5-d history of irritability, poor appetite, and respiratory distress. His presenting clinical symptoms were dyspnea, tachycardia, hypertension, and a palpable abdominal mass at the left upper quadrant. His troponin T and pro-B-type natriuretic peptide levels were elevated. Echocardiography demonstrated a dilated hypokinetic left ventricle with an ejection fraction of 29%, and a suspected left renal mass. Computed tomography scan revealed a left renal mass and multiple lung nodules. The definitive diagnosis of Wilms tumor was confirmed histologically. The patient was administered neoadjuvant chemotherapy and underwent radical nephrectomy. After surgery, radiotherapy was administered, and the adjuvant chemotherapy was continued. The blood pressure and left ventricular function normalized after the treatments. CONCLUSION Abdominal mass, dilated cardiomyopathy and hypertension can indicate Wilms tumor in pediatric patients. Chemotherapy and tumor removal achieve successful treatment.

Expression and significance of p53,nm23 and p16 in Wilms' tumor of children

We studied 22 Wilms’tumors of children immunohistochemically.We’ve found that the positive rate of p53 in slices was 31.8％ (7),of nm23 was 50％ (11),and of p16 was 86.4％ (19).It suggested that mutation rate of p53 was high in tumors,expression of nm23 in favorite histology(FH)was higher than that in unfavorite histology(UFH) group,and p16 showed very high positive rate in tumors.All of the three showed no relation with sex,age,or pathological type.So each one may be useful in clinic to evaluate pathogenesis and prognosis.

Discovery and identification of serum biomarkers of Wilms＇ tumor in mice using proteomics technology

Background Wilms＇ tumor （nephroblastoma） is a cancer of the kidneys that occurs typically in children and rarely in adults. Early diagnosis is very important for the treatment and prognosis of the disease. The aim of our study was to discover and identify potential non-invasive and convenient biomarkers for the diagnosis of Wilms＇ tumor. Methods Nude mice were used to construct a Wilms＇ tumor model by injecting nephroblastoma cells into their bilateral abdomen. We collected 94 serum samples from mice consisting of 45 samples with Wilms＇ tumor and 49 controls. The serum proteomic profiles of the samples were analyzed via surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The candidate biomarkers were purified by high-performance liquid chromatography, identified by liquid chromatography-mass spectrometry, and validated using ProteinChip immunoassays. Results We finally retrieved two differential proteins （mlz 4509.2; 6207.9）, which were identified as apolipoprotein A-II and polyubiquitin, respectively. The expression of apolipoprotein A-II was higher in the Wilms＇ tumor group than in the control group （P 〈0.01）. By contrast, the expression of polyubiquitin was lower in the Wilms＇ tumor group than in the control group. Conclusion Apolipoprotein A-II and polyubiquitin may be used as potential biomarkers for nephroblastoma in children, and the analysis of apolipoprotein A-II may help diagnose and treat Wilms＇ tumor.

Prognostic Impact of HER/2 Expression on Survival of Preoperatively Treated Children with Wilms Tumor at South Egypt

Aim: Wilms tumor (WT) is the most frequent type of pediatric renal tumors. Her/2 is an oncoprotein, its over-expression revealed to play a very vital role in the progress and improvement of certain tumors. This study evaluates the possible role of Her/2 as a prognostic indicator in formerly treated WT. Method: Immunohistochemical expression of Her/2 was studied in paraffin material of 40 WT patients followed SIOP 9 protocol. Patients’ medical records reviewed for clinical, pathological and outcome data and correlated with HER2 expression. Additional 15 samples of normal surrounding kidney tissue specimens were included. Results: Her/2 was often expressed in normal kidney tissue (renal tubules but not glomeruli) and at variable levels in the three elements of WT. At a median of 84 months, 70% of patients are living and under follow-up, surgical stage and pathologic subtypes were the only two factors significantly affect the outcome of our patients (p = 0.000, p = 0.007 & p = 0.004, p = 0.005 for OS (Overall survival) and DFS (Disease Free survival) respectively). Her/2 expression was associated with epithelial differentiation (p < 0.001). There was non-significant effect of Her/2 expression on OS or DFS of studied group. Conclusion: while the major progress in studying biology of WT, stage and pathological subtype continues the only predictive factors of significant value affecting the outcome of patients with WT. There was important association between Her/2 expression and histological differentiation in formerly treated Wilms tumor. Non-conclusive results regarding influence of Her/2 expression on the result of WT patients were found.

Juvenile myelo-monocytic leukemia (JMML): No effect of granulocyte monocyte-colony stimulating factor (GM-CSF) on Wilms Tumor gene (<i>WT</i>1) by nested Polymerase Chain Reaction (nPCR) and flow cytometry

This study was to determine whether GM-CSF induced WT1 gene expression and to establish an association with markers of proliferation CD71+CD34+ using nPCR and flow cytometry respectively, in samples obtained from 5 newly diagnosed JMML patients. Overtime (day 0 to day 14) there was an insignificant difference in WT1 gene expression and CD71+CD34+ in JMML samples when compared to peripheral blood of normal volunteers (n = 3). Our study suggests that there is a correlation between WT1 gene expression and cellular proliferation and that GMCSF in vitro does not create a significant difference in JMML samples.

Osteopathia striata with cranial sclerosis, Wilms' tumor and the WTX gene

Osteopathia striata with cranial sclerosis(OSCS, OMIM#300373) is an X-linked dominant sclerosing bone dysplasia that shows a distinct phenotype in females and males. In 2009, Zandra Jenkins et al found that germline mutations in the FAM123 B /WTX /AMER1 gene, mapped to chromosome Xq11.2, cause both the familial and sporadic forms of OSCS. Intriguingly, the WTX gene was already known as a putative tumor suppressor gene, since in 2007 Rivera et al had reported inactivating WTX mutations in Wilms' tumor(WT), the most frequent renal tumor of childhood. Here we review the heterogeneous clinical presentation of OSCS patients and the involvement of WTX anomalies in OSCS and in WT.

Survival Outcome of Wilms Tumor with Multi-Modality Treatment at Jimma Hospital, Southwest Ethiopia

Background: Wilms’ tumor (WT), the most common malignant neoplasm of the urinary tract of children [1], accounts for 5.9% of childhood cancers and affects one in every 10,000 children worldwide before the age of 15 years. The care of children with Wilm’s tumor in sub-Saharan Africa is compromised due to resource deficiencies that range from inadequate healthcare budgets to paucity of appropriately trained personnel. Childhood Wilms tumor is surging as an important paediatric problem in developing and sub-Saharan Africa countries. The objective of the study is to establish an understanding on the treatment challenges and outcomes of Wilm’s tumor in South West Ethiopia. Results: Forty-three Wilm’s tumor patients who were admitted from January 2017 to December 2021 were included in the study. The most frequent presentation was painless abdominal swelling in 40 (93%) patients. Fourteen patients (32.6%) were hypertensive at the time of diagnosis and the other 13 (30.2%) were normal. In abdominal examination, 31 (72.1%) patients had abdominal mass not crossing the midline and 12 (27.9%) had mass crossing the midline. After multimodal treatment, 37.5% had improvement, 11.6% came back with relapse. Most patients (41.7%) abandoned treatment and 9.3% of the cohort died in the course of treatment. Conclusion: The outcomes in the treatment of Wilms Tumor have been found to be poor in this review. The main reason for poor outcome has been not receiving adequate chemotherapy after surgery. Doses of chemotherapy received after surgery significantly affected treatment outcomes (p = 0.026).

Identification of a constitutional mutation in the WT1 gene in Taiwan Residents patients with Wilms tumor

The overall frequency of WT1 gene alterations in Wilms tumor is still unclear in Taiwan. Here we conducted molecular genetic analysis of the WT1 gene in Taiwan Residents patients with Wilms tumor. Polymerase chain reaction and direct sequencing were performed on DNA samples from blood and paraffin-embedded tumor specimens. A constitutional mutation in the WT1 gene was found in one DNA sample from peripheral blood lymphocytes. The remaining DNA samples from peripheral blood lymphocytes and paraffin-embedded tumor specimens were tested negative for both constitutional mutations and somatic mutations. Thus, mutations at other Wilms tumor loci may play an important role in Wilms tumor development.

Robotic approach with neoadjuvant chemotherapy in adult Wilms’ tumor: A feasibility study report and a systematic review of the literature

Objective:The incidence of Wilms’tumor(WT)among adult individuals accounts for less than 1%of kidney cancer cases,with a prognosis usually less favorable when compared to younger individuals and an overall survival rate of 70%for the adult patients versus 90%for the pediatric cases.The diagnosis and treatment of WT are complex in the preoperative setting;neoadjuvant chemotherapy(NAC)or robotic surgery has rarely been described.This study aimed to review the literature of robotic surgery in WT and report the first adult WT management using both NAC and robotic strategy.Methods:We reported a case of WT managed in a multidisciplinary setting.Furthermore,according to Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations,a systematic review of the literature until August 2020 of WT treated with a robotic approach was carried out.Results:A 33-year-old female had a diagnosis of WT.She was scheduled to NAC,and according to the clinical and radiological response to a robotic radical nephrectomy with aortic lymph nodes dissection,she was managed with no intraoperative rupture,a favorable surgical outcome,and a follow-up of 25 months,which did not show any recurrence.The systematic review identified a total number of 230 cases of minimally invasive surgery reported in the literature for WT.Of these,approximately 15 patients were carried out using robotic surgery in adolescents while none in adults.Moreover,NAC has not been administered before minimally invasive surgery in adults up until now.Conclusion:WT is a rare condition in adults with only a few cases treated with either NAC or minimally invasive approach so far.The advantage of NAC followed by the robotic approach could lead to favorable outcomes in this complex scenario.Notwithstanding,additional cases of adult WT need to be identified and investigated to improve the oncological outcome.