ABSTRACT
Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.
Subject(s)
Kidney Neoplasms/genetics , Kidney/metabolism , RNA, Messenger/genetics , RNA-Seq/methods , Single-Cell Analysis/methods , Transcriptome , Adult , Algorithms , Child , Fetus/metabolism , Gene Expression Regulation, Developmental , Humans , Kidney/embryology , Kidney Neoplasms/embryology , Kidney Neoplasms/metabolism , Models, Genetic , Signal Transduction/geneticsABSTRACT
RATIONALE: Fetal congenital mesoblastic nephroma (CMN) is a rare renal tumor, characterized by polyhydramnios, premature birth, and neonatal hypertension. In the prenatal stage, it is particularly difficult to diagnose CMN either by ultrasonography or magnetic resonance imaging (MRI). Thus, CMN is frequently detected in the third trimester in the clinical scenario. PATIENT CONCERNS: A 29-year-old G2P0 pregnant woman took routine prenatal examinations in our hospital. The fetal right kidney abnormality was not observed after 2 systematical ultrasonic examinations (at 24 and 31 weeks of gestation respectively), and only an increase was noticed in the amniotic fluid index (from 19.3 to 20.8âcm). DIAGNOSIS: CMN was detected by antenatal ultrasonography and MRI as a fetal right renal mass at 35 weeks of gestation in our hospital. INTERVENTIONS: The pregnant woman was admitted at a gestational age of 38 weeks and 5 days due to alterations in renal function. Further, the pregnant woman was administered with "oxytocin" to promote delivery, and the neonate underwent a right nephrectomy on the 9th day after birth. OUTCOMES: The pathological examination confirmed a cellular type of right CMN. The neonate recovered well after operation without adjuvant treatment. During 6 months of follow-up, the neonate grew well and showed no signs of recurrence or metastasis. CONCLUSION: Polyhydramnios detected during prenatal examination required attention due to the risk of malformation of fetal urinary system. Prenatal ultrasonography combined with MRI could not only clearly identify the origin of the tumor, but also distinguish the correlation between the tumor and adjacent structures, thereby leading to early diagnosis and favorable prognosis.
Subject(s)
Fetus/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Nephroma, Mesoblastic/diagnostic imaging , Ultrasonography, Prenatal/methods , Adult , Female , Gestational Age , Humans , Infant, Newborn , Kidney Neoplasms/embryology , Kidney Neoplasms/surgery , Multimodal Imaging , Nephrectomy , Nephroma, Mesoblastic/embryology , Nephroma, Mesoblastic/surgery , PregnancyABSTRACT
Cystic nephroma is a rare and benign renal tumour of unknown origin, usually diagnosed in the first years of childhood or during adult life. To our knowledge, there are no records in the literature of this particular tumour being descried prenatally. We present a case of a fetus diagnosed with cystic nephroma on 16 weeks of gestation. The renal tumour was evaluated by prenatal ultrasound, post mortem with 7T magnetic resonance imaging, and conventional autopsy.
Subject(s)
Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/embryology , Magnetic Resonance Imaging/methods , Nephroma, Mesoblastic/diagnostic imaging , Nephroma, Mesoblastic/embryology , Ultrasonography, Prenatal/methods , Diagnosis, Differential , Female , Humans , Kidney Neoplasms/pathology , Nephroma, Mesoblastic/pathology , Pregnancy , Pregnancy Trimester, SecondABSTRACT
Imaging plays a key role in the diagnosis and staging of prenatal and neonatal tumors, and is essential in treatment planning. Though obstetrical ultrasound is the first choice prenatally, fetal MRI continues to play an increasing role as experience with this imaging modality increases. In the neonate, in addition to ultrasound and MRI, CT and nuclear medicine studies can also play an important role. We describe the prenatal and neonatal imaging findings of some of the most common congenital abdominal and soft tissue neoplasms including neuroblastoma, renal, liver and soft tissue tumors.
Subject(s)
Abdomen/pathology , Kidney Neoplasms/diagnosis , Liver Neoplasms/diagnosis , Magnetic Resonance Imaging , Neuroblastoma/diagnosis , Prenatal Diagnosis , Soft Tissue Neoplasms/diagnosis , Female , Humans , Infant, Newborn , Kidney Neoplasms/embryology , Kidney Neoplasms/therapy , Liver Neoplasms/embryology , Liver Neoplasms/therapy , Neuroblastoma/congenital , Neuroblastoma/embryology , Neuroblastoma/therapy , Pregnancy , Prognosis , Soft Tissue Neoplasms/embryology , Soft Tissue Neoplasms/therapyABSTRACT
Congenital anomalies of the upper urinary tract are common and frequently diagnosed on prenatal ultrasound. In the absence of infection, these anomalies are often asymptomatic. This article reviews key features and long-term implications to assist in discussions with families. In contrast, a perinatal renal tumor is rare but extremely alarming. This update on the most common tumors and their treatment is useful in reassuring parents that most infants, after primary surgical resection, are cured without adjuvant therapies. To understand renal agenesis and other congenital renal malformations and their associated anomalies, a brief review of normal renal development is presented.
Subject(s)
Kidney Neoplasms , Urinary Tract/abnormalities , Urogenital Abnormalities/diagnosis , Female , Global Health , Humans , Incidence , Infant, Newborn , Kidney Neoplasms/diagnosis , Kidney Neoplasms/embryology , Kidney Neoplasms/epidemiology , Pregnancy , Prenatal Diagnosis , Urogenital Abnormalities/epidemiologyABSTRACT
Clear cell sarcoma of the kidney (CCSK) is a tumor affecting children with a median age of 3 years at diagnosis. The cell of origin of CCSK is unknown and data on the molecular changes giving rise to CCSK is scarce. This has hindered the identification of positive diagnostic markers and development of molecularly targeted treatment protocols for CCSK. We have characterized a panel of CCSK to gain information regarding its molecular profile and possible origin. High-resolution genomic analysis with single nucleotide polymorphism array of 37 tumors did not reveal any clues to the mechanisms behind tumor development as remarkably few genetic imbalances were found. Gene expression analysis revealed a highly characteristic gene signature, enriched for pathways involved in embryonic development, including kidney formation. The presence of markers for two different developmental lineages in the embryonic kidney was therefore investigated in the tumor cells. FOXD1 which identifies cells giving rise to stromal elements, and CITED1, a marker for cells primed for nephrogenic epithelial differentiation, were both highly expressed in CCSK. In addition, the early embryonic marker OSR1 was expressed at higher levels in CCSK than in Wilms tumor, normal fetal kidney or adult kidney. As this marker discriminates the intermediate mesoderm from other mesodermal structures, our study could suggest that CCSK arises from a mesodermal cell type that retains the capacity to initiate differentiation towards both nephrons and stroma, but remains locked in a primitive state.
Subject(s)
Kidney Neoplasms/genetics , Kidney/pathology , Sarcoma, Clear Cell/genetics , Apoptosis Regulatory Proteins , Child , Child, Preschool , Female , Forkhead Transcription Factors/genetics , Gene Expression Profiling , Humans , Infant , Kidney/embryology , Kidney Neoplasms/embryology , Male , Nuclear Proteins/genetics , Paraffin Embedding , Polymorphism, Single Nucleotide , Sarcoma, Clear Cell/embryology , Signal Transduction , Trans-Activators , Transcription Factors/geneticsABSTRACT
Various fetal or placental disorders cause Ballantyne's (mirror) syndrome. For the first time, we report a maternal manifestation of Ballantyne's syndrome occurring concomitantly with the development of fetal congenital mesoblastic nephroma (CMN). In a pregnant woman with a CMN fetus, lung edema, hypertension, hyperthyroidism, and high serum human chorionic gonadotrophin level occurred, all of which characterize maternal manifestation of Ballantyne's syndrome. The fetus and placenta were devoid of 'edema', lacking 'triple edema', and thus this condition was not diagnosed as Ballantyne's syndrome; however, we considered this condition as the maternal manifestation of Ballantyne's syndrome. We performed emergent cesarean section at 28 weeks. Delivery acutely ameliorated maternal symptoms. Tumor was resected and was confirmed as CMN. Maternal manifestations of Ballantyne's syndrome, such as lung edema and hypertension, can occur in a mother with fetal CMN even without fetal and/or placental edema. The clinical course of this patient may suggest an etiology of Ballantyne's syndrome.
Subject(s)
Hydrops Fetalis/diagnosis , Hyperthyroidism/diagnosis , Kidney Neoplasms/embryology , Nephroma, Mesoblastic/embryology , Pregnancy Complications/diagnosis , Prenatal Diagnosis , Pulmonary Edema/diagnosis , Adult , Cesarean Section , Chorionic Gonadotropin/blood , Diagnosis, Differential , Female , Humans , Hypertension, Pregnancy-Induced/blood , Hypertension, Pregnancy-Induced/diagnosis , Hypertension, Pregnancy-Induced/therapy , Hyperthyroidism/blood , Hyperthyroidism/complications , Hyperthyroidism/therapy , Infant, Newborn , Kidney Neoplasms/complications , Kidney Neoplasms/diagnosis , Kidney Neoplasms/surgery , Nephroma, Mesoblastic/complications , Nephroma, Mesoblastic/diagnosis , Nephroma, Mesoblastic/surgery , Pre-Eclampsia/diagnosis , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/therapy , Pulmonary Edema/blood , Pulmonary Edema/complications , Pulmonary Edema/therapy , Syndrome , Treatment Outcome , Up-RegulationABSTRACT
Mesoblastic nephroma is by far the most frequent intrarenal fetal tumor. To the best of our knowledge, we report the first case of a newborn with an intrarenal neuroblastoma that was discovered prenatally. An intrarenal echogenic and homogenous mass was observed on routine prenatal ultrasonography, corroborated by magnetic resonance imaging, in a 30-week gestation fetus. A male weighing 3280 g was born with elevated blood pressure and cardiac failure. Postnatal ultrasound confirmed a left intrarenal tumor with microcalcifications and perirenal adenopathy. An open total left nephrectomy by laparotomy was performed. The pathologic study reported that the mass was an intrarenal neuroblastoma with local and regional invasion. Immediate postoperative urine analysis revealed a high level of vanillylmandelic acid, and blood samples showed high levels of normetanephrine. The purpose of this report is to demonstrate that prenatal intrarenal neuroblastoma can clinically and radiologically mimick a mesoblastic nephroma. High blood pressure, calcifications, and lymphadenopathy on ultrasound should raise the index of suspicion for a possible malignant process. Preoperative measurement of urinary vanillylmandelic acid (VMA) and metanephrines should be performed if the diagnosis is in doubt.
Subject(s)
Diagnostic Errors , Kidney Neoplasms/embryology , Nephroma, Mesoblastic/diagnosis , Neuroblastoma/embryology , Ultrasonography, Prenatal , Biomarkers, Tumor/urine , Calcinosis/congenital , Calcinosis/etiology , Cesarean Section , Heart Failure/congenital , Heart Failure/etiology , Humans , Hypertension, Renal/congenital , Hypertension, Renal/etiology , Infant, Newborn , Kidney Neoplasms/complications , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Kidney Neoplasms/urine , Liver Neoplasms/secondary , Magnetic Resonance Imaging , Male , Nephrectomy , Neuroblastoma/complications , Neuroblastoma/diagnostic imaging , Neuroblastoma/pathology , Neuroblastoma/secondary , Neuroblastoma/surgery , Neuroblastoma/urine , Normetanephrine/urine , Vanilmandelic Acid/urineABSTRACT
Agents that can enhance tumor cell apoptosis and inhibit invasion have potential for the treatment of cancer. Here, we report the identification of escin, a pentacyclic triterpenoid from horse chestnut that exhibits antitumor potential against leukemia and multiple myeloma. Whether examined by esterase staining, phosphatidyl-serine staining, DNA breakage, or caspase-mediated poly(ADP-ribose) polymerase cleavage, escin potentiated tumor necrosis factor (TNF)-induced apoptosis but inhibited tumor cell invasion. This correlated with the down-regulation of bcl-2, cellular inhibitor of apoptosis protein-2, cyclin D1, cyclooxygenase-2, intercellular adhesion molecule-1, matrix metalloproteinase-9, and vascular endothelial growth factor, which are all regulated by the activation of the transcription factor NF-kappaB. When examined by electrophoretic mobility shift assay, the triterpenoid suppressed nuclear factor-kappaB (NF-kappaB) activation induced by TNF and other inflammatory agents, and this correlated with the inhibition of IkappaBalpha phosphorylation and degradation, inhibition of IkappaB kinase complex (IKK) activation, suppression of p65 phosphorylation and nuclear translocation, and abrogation of NF-kappaB-dependent reporter activity. Overall, our results demonstrate that escin inhibits activation of NF-kappaB through inhibition of IKK, leading to down-regulation of NF-kappaB-regulated cell survival and metastatic gene products and thus resulting in sensitization of cells to cytokines and chemotherapeutic agents.
Subject(s)
Escin/pharmacology , NF-kappa B/antagonists & inhibitors , Annexin A5/metabolism , Apoptosis/drug effects , Cell Line, Tumor , DNA Primers , Gene Expression Regulation , Genes, Reporter , Humans , Kidney Neoplasms/embryology , Kidney Neoplasms/pathology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Mutagenesis , NF-kappa B/drug effects , NF-kappa B/genetics , Neoplasm Invasiveness , Signal Transduction/drug effects , Transcription, Genetic/drug effectsABSTRACT
PURPOSE: We established a vitamin A-deficient (VAD) model of pregnant rats to evaluate the effect of vitamin A deficiency in maternal rats on tumor formation in filial rats. METHODS: Ten pregnant Wistar rats were divided into 2 groups: (1) VAD group, 6 rats were given nonvitamin A diet from 2 weeks before mating till delivery and (2) normal diet (ND) group, 4 rats were given normal diet. Twenty random neonatal rats from each group were killed on the next day of delivery. The rest neonates were given normal diet for 1 year until killed. Serum levels of vitamin A, morphology of the kidney, incidence of tumor formation, and retinoid X receptor (RXR) alpha messenger RNA (mRNA) expression in renal tissue were assessed for the filial rats. RESULTS: Fifty-six and 49 neonatal rats were born for VAD group and ND group, respectively. The detection rate of nephrogenic rests (NRs) from neonates in VAD group (50%) was significantly higher than that in ND group (20%; P < .05). The incidence of nephroblastoma was 13.9% in filial rats of VAD group and 0% for ND group. The detection rate of NRs for filial rats of VAD group (30.6%) was significantly higher than that of ND group (6.9%; P < .01). The expression of RXRalpha mRNA in tumor tissue of the filial rats of VAD group (3.17 +/- 0.15) was significantly lower than that in kidney tissue of ND group (3.58 +/- 0.20; P < .01). CONCLUSION: Deficiency in vitamin A for pregnant rats resulted in renal dysplasia, increased NRs, and higher incidence of nephroblastoma.
Subject(s)
Kidney Neoplasms , Prenatal Exposure Delayed Effects , Vitamin A Deficiency/complications , Wilms Tumor , Animals , Animals, Newborn , Diet , Disease Models, Animal , Female , Kidney Glomerulus/pathology , Kidney Neoplasms/embryology , Kidney Neoplasms/pathology , Kidney Neoplasms/physiopathology , Kidney Tubules/pathology , Male , Pregnancy , Prenatal Exposure Delayed Effects/physiopathology , Rats , Rats, Wistar , Retinoid X Receptors/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Vitamin A Deficiency/pathology , Vitamin A Deficiency/physiopathology , Wilms Tumor/chemically induced , Wilms Tumor/embryology , Wilms Tumor/pathology , Wilms Tumor/physiopathologySubject(s)
Kidney Neoplasms/embryology , Ureter/embryology , Wilms Tumor/embryology , Fetus/embryology , Fetus/metabolism , Fetus/pathology , Gene Expression , Humans , Immunohistochemistry , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Kidney/abnormalities , Kidney/embryology , Kidney/metabolism , Kidney/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Receptors, Immunologic/genetics , Receptors, Immunologic/metabolism , Ureter/pathology , Wilms Tumor/genetics , Wilms Tumor/metabolism , Wilms Tumor/pathology , Roundabout ProteinsABSTRACT
While the activity of Snail genes is required during embryonic development for the formation of different tissues and organs, they must be repressed in the adult in order to maintain epithelial integrity and homeostasis. Indeed, pathological activation of Snail in epithelial tumors induces malignancy and the recurrence of tumors. Here we show that in dedifferentiated areas of human renal carcinomas, Snail undergoes a process of reactivation. In addition to tumor progression, renal fibrosis is also linked to the activity of Snail genes and indeed, reactivation of Snail in the adult kidney is sufficient to induce fibrosis. Thus, Snail genes illustrate a paradigm whereby reactivation of crucial embryonic genes in adult tissues provokes the onset of devastating diseases.
Subject(s)
Carcinoma/embryology , Embryonic Development/genetics , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/embryology , Kidney/embryology , Kidney/pathology , Transcription Factors/genetics , Transcription Factors/metabolism , Animals , Carcinoma/genetics , Carcinoma/pathology , Fibrosis , Gene Expression Regulation, Neoplastic/physiology , Humans , Kidney/metabolism , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Snail Family Transcription FactorsABSTRACT
The von Hippel-Lindau tumor suppressor pVHL plays a critical role in the pathogenesis of familial and sporadic clear cell carcinomas of the kidney and hemangioblastomas of the retina and central nervous system. pVHL targets the oxygen sensitive alpha subunit of hypoxia-inducible factor (HIF) for proteasomal degradation, thus providing a direct link between tumorigenesis and molecular pathways critical for cellular adaptation to hypoxia. Cell type specific gene targeting of VHL in mice has demonstrated that proper pVHL mediated HIF proteolysis is fundamentally important for survival, proliferation and differentiation of many cell types and furthermore, that inactivation of pVHL may, unexpectedly, inhibit tumor growth under certain conditions. Mouse knock out studies have provided novel mechanistic insights into VHL associated tumorigenesis and established a central role for HIF in the development of the VHL phenotype.
Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Disease Models, Animal , Fetal Development/physiology , Gene Targeting , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Von Hippel-Lindau Tumor Suppressor Protein/physiology , Animals , Carcinoma, Renal Cell/embryology , Carcinoma, Renal Cell/pathology , Fetal Development/genetics , Gene Targeting/methods , Kidney Neoplasms/embryology , Kidney Neoplasms/pathology , Mice , Mice, Knockout , Von Hippel-Lindau Tumor Suppressor Protein/antagonists & inhibitors , Von Hippel-Lindau Tumor Suppressor Protein/geneticsABSTRACT
INTRODUCTION: Wilms' tumor (WT) is the most frequent embryonic renal neoplasia in children. OBJECTIVE: This study was carried out to investigate risk factors in the development of WT. MATERIAL AND METHODS: A design of cases and controls, proactive, of incident cases, with four controls per case. The study population of cases were children of two oncologic reference Center of the Mexican Institute of Social Security (IMSS) in the Mexican Federal District during 5-year period. For the control group, children were frequency matched by age and sex at with cases from the same clinic. A questionnaire, previously validated, was applied to determine risk factors in both groups. RESULTS: During the period of study, 34 cases and 136 controls were revised. Significant risk factors were: antecedent of a relative with Down syndrome (OR = 7.6, 95%CI 1.4-51.1, p = 0.008), eczema (OR = 3.7, 95%Cl 1.1-12, p = 0.01); having been conceived in autumn (OR = 5.4, 95%CI 1.3-31.6, p = 0.007) or winter (OR = 4.9, 95%Cl 1.1-29.9, p = 0.01), and beet ingestion (OR = S. 7, 95%Cl 1.7-19.4, p = 0.0007). CONCLUSIONS: In this study, influence of prenatal factors are shown and we attempt to explain the etiology of WT, the important of beet ingestion, and conclusions suggest that that more epidemiologic studies are necessary to determine the chain of events that causes Wilms' tumor.
Subject(s)
Wilms Tumor/etiology , Adolescent , Beta vulgaris/adverse effects , Case-Control Studies , Child , Child, Preschool , Diet/adverse effects , Down Syndrome/complications , Eczema/complications , Female , Gestational Age , Humans , Incidence , Kidney Neoplasms/embryology , Male , Maternal Age , Maternal Exposure/adverse effects , Maternal Exposure/statistics & numerical data , Maternal Welfare/statistics & numerical data , Mexico/epidemiology , Occupational Exposure/adverse effects , Occupational Exposure/statistics & numerical data , Risk Factors , Seasons , Socioeconomic Factors , Wilms Tumor/epidemiologyABSTRACT
PURPOSE: The recent basic science literature is replete with new discoveries in the molecular genetics of renal development. However, little of this information has filtered into urological textbooks and journals. An effort is made herein to integrate these new findings and propose a more sophisticated blueprint of renal development than the one traditionally taught in medical school and residency. To accomplish this goal the author offers simple definitions and interpretations of complicated terms and events, and points out how maldevelopment results when mutations take place. MATERIALS AND METHODS: A review of recent advances in the molecular genetics of renal development and maldevelopment was done. RESULTS: Renal metanephric development results from the expression of many genes in the ureteral bud and metanephric blastema with each sending messages to the other to induce organogenesis. CONCLUSIONS: Currently an understanding of normal renal organogenesis stems from a study of disease states resulting from perturbations in molecular genetics. In turn, a better understanding of normal renal organogenesis facilitates an understanding of how dysplasia, hypoplasia, cystic disease and tumors develop when molecular genetics go awry. For each form of renal dysgenesis and for most renal tumors 1 or more gene defects are eventually identified. The young urologist based in these new discoveries would be better prepared to make the breakthroughs in the future that are necessary for advancing the prevention and management of these conditions.
Subject(s)
Gene Expression Regulation, Developmental , Genes , Kidney/abnormalities , Kidney/embryology , Mutation , Zebrafish Proteins , Animals , Cell Differentiation/genetics , Genes, Homeobox/genetics , Growth Substances/genetics , Humans , Kidney Neoplasms/embryology , Molecular Biology , Proto-Oncogene Proteins/genetics , Renin-Angiotensin System/genetics , Transcription Factors/genetics , Ureter/embryology , Wnt ProteinsABSTRACT
This article discusses the embryology and anatomy of the kidney and ureter. Surgical approaches, such as the lumbar and thoracoabdominal, are provided. Operations for kidney (i.e., radical nephrectomy, nephroureterectomy, and partial nephrectomy) and ureteric tumors also are discussed.
Subject(s)
Kidney Diseases/surgery , Kidney Neoplasms/surgery , Ureteral Diseases/surgery , Ureteral Neoplasms/surgery , Humans , Kidney/embryology , Kidney/pathology , Kidney/surgery , Kidney Diseases/embryology , Kidney Diseases/pathology , Kidney Neoplasms/embryology , Kidney Neoplasms/pathology , Nephrectomy , Ureter/embryology , Ureter/pathology , Ureter/surgery , Ureteral Diseases/embryology , Ureteral Diseases/pathology , Ureteral Neoplasms/embryology , Ureteral Neoplasms/pathologyABSTRACT
The fetal kidney is formed by the development of nephrons from fetal metanephric blastema surrounding the ureteric bud. The fetal renal tissue matures into normal renal parenchyma during gestation, but, occasionally, fetal tissue persists into infancy as microscopic foci called nephrogenic rests. Nephrogenic rests are found in approximately 1% of infant kidneys at autopsy. Nephrogenic rests are associated with an increased risk of Wilms tumor, and it is theorized that nephrogenic rests undergo neoplastic change into Wilms tumor. Fortunately, this transformation occurs in less than 1% of young children with nephrogenic rests. Nephrogenic rests are associated with many syndromes, including Beckwith-Wiedemann syndrome, hemihypertrophy, and sporadic aniridia. Children with identifiable syndromes, once diagnosed, should be screened for the development of Wilms tumor. Nephrogenic rests are associated with other lesions such as multilocular cystic nephroma and multicystic dysplasia, usually without malignant complications.
Subject(s)
Kidney Diseases/diagnosis , Kidney Neoplasms/diagnosis , Nephrons , Precancerous Conditions/diagnosis , Wilms Tumor/diagnosis , Beckwith-Wiedemann Syndrome/diagnosis , Beckwith-Wiedemann Syndrome/embryology , Beckwith-Wiedemann Syndrome/pathology , Child , Child, Preschool , Choristoma/diagnosis , Choristoma/embryology , Choristoma/pathology , Diagnostic Imaging , Female , Humans , Infant , Infant, Newborn , Kidney/embryology , Kidney/pathology , Kidney Diseases/embryology , Kidney Diseases/pathology , Kidney Neoplasms/embryology , Kidney Neoplasms/pathology , Male , Precancerous Conditions/embryology , Precancerous Conditions/pathology , Pregnancy , Wilms Tumor/embryology , Wilms Tumor/pathologyABSTRACT
The development of a complex tissue from a few simple precursor cells requires the precise activation and repression of tissue-specific genes that determine cell lineages, tissue patterning, and cellular proliferation. In the kidney, a number of recently identified genes are critical for normal development. Among these, the Pax-2 gene encodes a transcription factor that is expressed in the ureter bud, in the induced kidney mesenchyme, and in the progenitor cells of the glomerular and tubular epithelium. Although the differentiation of the renal epithelium requires Pax-2 function, failure to suppress the gene in mature epithelium is detrimental to normal renal function. Recent, data suggest that the Wilms' tumor-suppressor gene WT1 can down-regulate Pax-2 expression, consistent with high levels of Pax-2 in Wilms' tumors. Additional studies suggest that reactivation of this developmental regulator can contribute to a variety of other renal diseases.
Subject(s)
DNA-Binding Proteins/genetics , Kidney Neoplasms/genetics , Kidney/embryology , Transcription Factors/genetics , Cell Differentiation , Cell Division , Cell Lineage , Down-Regulation , Epithelium/embryology , Gene Expression Regulation, Neoplastic , Genes, Wilms Tumor/genetics , Humans , Kidney/growth & development , Kidney Glomerulus/embryology , Kidney Neoplasms/embryology , Kidney Tubules/embryology , Mesoderm/metabolism , PAX2 Transcription Factor , Ureter/embryology , WT1 Proteins , Wilms Tumor/genetics , Zinc Fingers/geneticsABSTRACT
The specificity of IGF2 promoter imprinting was examined in embryonal tissues and Wilms tumour. In several fetal tissues of approximately 12 weeks gestation, IGF2 was found to be monoallelically expressed from all IGF2 promoters i.e. P1, P2, P3 and P4. However, in tissues of slightly older gestation age (15-17 weeks) relaxation of imprinting at the P1 promoter was evident, although the P2-P4 promoters remained imprinted. These data indicate that early in embryogenesis a population of cells exists in which all IGF2 promoters are imprinted, but that as development proceeds the imprinting of the P1 promoter is relaxed. The pattern of IGF2 promoter imprinting was also analysed in Wilms tumour. In some tumours, the pattern of promoter imprinting was identical to that found in early fetal kidney, indicating that this tumour originates within early embryonic kidney tissue. In contrast, in tumours in which relaxation of imprinting had occurred, imprinting relaxation affected all IGF2 promoters. This aberrant pattern of promoter imprinting, which was not detected in fetal kidney, provides further evidence that pathological relaxation of IGF2 imprinting is involved in the genesis of Wilms tumour.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 11 , Embryonic and Fetal Development , Insulin-Like Growth Factor II/genetics , Kidney Neoplasms/embryology , Kidney Neoplasms/genetics , Promoter Regions, Genetic , Wilms Tumor/embryology , Wilms Tumor/genetics , Adult , Base Sequence , Chromosome Mapping , DNA Primers , Exons , Female , Humans , Kidney/embryology , Kidney/pathology , Molecular Sequence Data , Polymerase Chain Reaction , Polymorphism, Genetic , Pregnancy , Transcription, GeneticABSTRACT
The development of a complex, multicellular organ, such as the kidney, from two embryonic progenitor tissues requires the activation and suppression of transcription factors that regulate tissue and cell type-specific gene expression. From areas as diverse as fruit fly development and human cancer genetics, a number of important genes have been identified that help to orchestrate the early events of renal epithelium induction and differentiation. The Wilms' tumor-suppressor gene WT1 is critical for regulating the early response of the kidney mesenchyme to induction and may play multiple roles during the course of renal epithelial cell development and tumor formation. The Pax-2 gene is activated in the mesenchyme after induction and is necessary for condensation and perhaps proliferation of the induced cells. How these two important gene products exert their effects will be discussed in light of recent evidence on DNA binding, transcription repression, and protein interactions.