Cases reported "Kidney Neoplasms"

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1/16. High incidence of cancer in a family segregating a mutation of the ATM gene: possible role of ATM heterozygosity in cancer.

    ATM mutations predispose cells to malignancy by promoting chromosomal instability. We have identified a family with multiple cancers that segregates a mutant allele of ATM, IVS61 2insTA, which causes skipping of exon 61 in the mRNA, as well as a previously undescribed polymorphism, IVS61 104C(54):T(46). The mutation was inherited by two sisters, one who developed breast cancer at age 39 and the second at age 44, from their mother, who developed kidney cancer at age 67. Molecular studies were undertaken to determine the role of the ATM gene in the development of cancer in this family. Studies of irradiated lymphocytes from both sisters revealed elevated numbers of chromatid breaks, typical of A-T heterozygotes. Studies on lymphoblastoid cell lines established from these individuals revealed abnormal p53 induction and apoptosis after dna damage. Loss of heterozygosity (LOH) in the ATM region of chromosome 11q23.1 showed that the normal ATM allele was lost in the breast tumor of the older sister. LOH was not seen at the BRCA1 or BRCA2 loci. BRCA2 is not likely to be a cancer-predisposing gene in this family because each sister inherited different chromosomes 13 from each parent. The sisters share their maternal BRCA1 allele, although no mutation in this gene was detected in the family. Our findings suggest that haploinsufficiency at ATM may promote tumorigenesis, even though LOH at the locus supports a more classic two-hit tumor suppressor gene model.
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ranking = 1
keywords = tumorigenesis
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2/16. Tissue-specific expression of SV40 in tumors associated with the li-fraumeni syndrome.

    Inactivation of wild-type p53 tumor suppressor function is the primary mechanism of tumor initiation in li-fraumeni syndrome (LFS) individuals with germline p53 mutations. Tumors derived from LFS patients frequently retain the normal p53 allele, suggesting that alternative mechanisms in addition to gene deletion must be involved in inactivating wild-type p53 protein. dna tumor viruses, such as SV40, target p53 for inactivation through the action of viral oncoproteins. We studied the probands from two unrelated LFS families, each of whom presented with multiple malignant neoplasms. Patient 1 developed an embryonal rhabdomyosarcoma (RMS) and a choroid plexus carcinoma (CPC), while patient 2 developed a CPC and subsequently presented with both an osteosarcoma (OS) and renal cell carcinoma (RCC). We utilized DNA sequence analysis and immunohistochemistry to determine p53 gene status in the germline and tumors, as well as evidence for SV40 T-antigen oncoprotein expression. Each patient harbored a heterozygous germline p53 mutation at codons 175 and 273, respectively. In patient 1, the normal p53 gene was lost while the mutant p53 allele was reduced to homozygosity in the RMS. Both normal and mutant genes were maintained in the CPC. In patient 2, normal and mutant p53 alleles were retained in both the CPC and RCC. Both specific PCR and immunostaining detected SV40 T-antigen in both CPCs and the RCC. In addition to chromosomal alterations, epigenetic mechanisms may disrupt p53 function during tumorigenesis. In two LFS patients, we found SV40 DNA sequences and viral T-antigen expression that could account for inactivation of the normal p53 protein. Inactivation of p53 or other tumor suppressors by viral proteins may contribute to tumor formation in specific tissues of genetically susceptible individuals.
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ranking = 1
keywords = tumorigenesis
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3/16. A novel WT1 gene mutation associated with wilms' tumor and congenital male genitourinary malformation.

    WT1 is located on the short arm of human chromosome 11 and consists of 10 coding exons. Mutations of this gene have been reported to be the cause of Wilms' tumor, congenital male genitourinary malformations, and/or renal disorders. We describe here a novel WT1 gene mutation, i.e. a point mutation at intron 7 ( 2) in both the tumor and the germline cells of a patient with Wilms' tumor and congenital male genitourinary malformation, but without renal disorder. The position of the mutation is at a splice donor site of intron 7, which causes the splicing out of exon 7 and generates a truncated protein. This type of mutation in the WT1 zinc finger domain has not been reported before. The mutation is of paternal origin and is heterozygous in the germline cells. In the tumor cells, however, the maternal allele is largely lost, from 11p12 to 11p15, which results in maternal loss of heterozygosity. These results, together with the data from previous reports, suggest that WT1 may function in gonadogenesis, nephrogenesis, and Wilms' tumor tumorigenesis.
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ranking = 1
keywords = tumorigenesis
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4/16. Incidentally detected nephrogenic rests in the setting of congenital obstructive uropathy.

    PURPOSE: Nephrogenic rests (NR) are clusters of cells similar to renal blastema. NR are frequently seen in kidneys with Wilms' tumor (WT) and are seen with higher frequency in nephrectomy specimens from obstructed and/or multicystic dysplastic kidneys (MCDK) compared to autopsy series of normal kidneys. The significance of NR and their role in tumorigenesis is largely unknown. We report the findings of two cases with NR associated with ureteral ectopy/obstruction and review the relevant literature. MATERIALS AND methods: Two cases of upper pole heminephrectomy associated with ectopic upper pole ureter and resultant hydronephrosis were found to have nephrogenic rests present on pathologic examination. A literature search was done to review recent developments in the understanding of NR and their significance, primarily to guide patient recommendations regarding follow-up. RESULTS: Recent developments in the understanding of NR include the description of intralobar versus perilobar nephrogenic rests and prognostic considerations associated with each. However, the implications of finding nephrogenic rests in upper pole hemi-nephrectomy specimens associated with ureteral ectopy is not well delineated. CONCLUSIONS: The role of NR in tumorigenesis is still poorly understood. Because of the still undefined relationship with WT we recommend patients with incidentally detected NR be followed with serial abdominal ultrasounds for the first 5 years of life.
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ranking = 2
keywords = tumorigenesis
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5/16. Characterization of a wilms tumor in a 9-year-old girl with trisomy 18.

    This is a report of a trisomy 18 patient who developed wilms tumor in conjunction with perilobar nephroblastomatosis (NB) at 9 years and 5 months of age. review of the literature revealed that most patients with trisomy 18 who develop wilms tumor, do so at a later than expected age for a tumor related to NB, and are females. In this case, no chromosome 11 WT1 mutation was detected by PCR/SSCP analysis, but the tumor had in addition to the trisomy, an isochromosome 7q and loss of heterozygosity at 16q, two mutations that have been linked independently to Wilms tumorigenesis.
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ranking = 1
keywords = tumorigenesis
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6/16. Low-grade renal epithelial tumor originating from the distal nephron.

    There are few published reports of low-grade renal epithelial tumor originating from the distal nephron. However, it should not be disregarded clinically, because the actual number of patients with such tumors may be higher than expected. We investigated the immunohistochemical profile of a histologically distinct subtype of such a tumor in detail, in addition to the clinical course and imaging studies. The present study demonstrated that both glandular and spindle cell components of this tumor have a persistent characteristic of an epithelial tumor arising from the distal tubule or collecting duct. This tumor is a benign complex neoplasm that can be treated successfully with radical surgery. Beta-catenin and E-cadherin are suggested to play a crucial role in tumorigenesis and the biphasic arrangement of this neoplasm, concerning the expression of epithelial membrane antigen and carbohydrate antigen 19-9. We suggest that the term 'distal nephron epithelioma' is appropriate for classifying such rare but clinicopathologically distinct tumors.
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ranking = 1
keywords = tumorigenesis
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7/16. Linking human genetics with molecular medicine: will hereditary renal cancer play a major role?

    An inherited or familial predisposition to form kidney tumors represents less than 4% of all renal malignancies. However, hereditary renal cancer (HRC) syndromes offer important opportunities for gene discovery and function. Basic and clinical HRC investigation often provides unique insight into regulation of cell growth, cell proliferation, tumor invasion and metastasis. The genetics, biochemistry and physiology of renal tumorigenesis has been directly impacted and significantly expanded by HRC research over the last ten years. Mutations have been identified in several genes tightly linked to increased risk for development of renal cancer. Inheritance of these mutated genes causes specific hereditary syndromes often associated with clinically significant nonrenal manifestations. Molecular and biochemical alterations of most HRC gene products are also detected in sporadic renal cancer emphasizing the importance of HRC gene function in nonhereditary carcinogenesis. Despite these important molecular findings, the clinical contribution of HRC research has generally been limited to genetic screening and prognostic assessment. HRC patients and their physicians continue to face difficult decisions regarding cancer control and quality of life despite advances in minimally invasive surgical and radiological techniques. The ultimate challenge for clinicians and scientists will be translation of molecular and genetic research into clinical tools that impact diagnosis, treatment and prevention. This bench to bedside report describes the diagnosis, genetics, pathophysiology and current cancer treatment options available for HRC syndromes.
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ranking = 1
keywords = tumorigenesis
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8/16. gene expression profiling of mesoblastic nephroma and Wilms tumors--comparison and clinical implications.

    OBJECTIVES: To better understand the molecular mechanisms in the tumorigenesis and progression of mesoblastic nephroma (MN), we studied its gene expression profiles. MN is the most common tumor of the neonatal kidney. It occurs in a younger age group than the wilms tumor (WT). To date, very little is known about the etiology and pathogenesis of MN. methods: Using microarrays containing 22,943 cDNA, we analyzed the expression profiles of MN and compared its expression profiles with those of several other types of kidney tumors, including WT. RESULTS: MN has a distinct molecular signature that clusters close to the WT, suggesting that both types of tumor share some similarity in gene expression and biology. When comparing the two profiles closely, we identified a number of genes that are commonly upregulated in both tumors, including insulin-like growth factor 2, thrombospondin 4, and mesenchyme homeo box 1. We also identified a set of genes that distinguish MN from WT, some of which may underlie the difference in their behaviors and can be used as diagnostic markers. Among this group of genes, topoisomerase II-alpha, highly expressed in WTs, is not overexpressed in MN. Immunohistochemical staining of topoisomerase II-alpha in additional cases of WTs and MNs confirmed this distinction further. CONCLUSIONS: The results of our study demonstrated that MN has a distinct gene expression profile and that some of the newly identified genes can be potentially used as novel diagnostic markers.
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ranking = 1
keywords = tumorigenesis
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9/16. Tumor in the horseshoe kidney: clinical implications and review of embryogenesis.

    We report on 3 patients with tumor in a horseshoe kidney, 1 of whom had bilateral tumor (renal cell cancer on the right side and urothelial cancer on the left side). Tumors that arise predominantly in the bridge of a horseshoe kidney can mimic the symptoms of an intra-abdominal disease process. Besides routine diagnostic procedures, angiography is essential to plan the surgical approach, which in principle should be organ-sparing. The literature of the embryology of the horseshoe kidney was reviewed for a relationship between the abnormal renal development and the site of tumorigenesis, and for development of a key for the wide variation of blood supply. Recently reported data suggest that the theory of a mechanical fusion is valid only for horseshoe kidneys with a fibrous isthmus but that an abnormal migration of the posterior nephrogenic area causes the majority of horseshoe kidneys in which the isthmus consists of parenchyma. Development of the isthmus through abnormal migration could predispose this location for renal cell cancer and would explain the varying forms of blood supply. Additionally, this hypothesis supports the previously raised assumption that horseshoe kidneys may be the result of teratogenic factors, which also may be responsible for the known increased incidence of related congenital anomalies and of nephroblastoma.
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ranking = 1
keywords = tumorigenesis
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10/16. Novel familial WT1 read-through mutation associated with wilms tumor and slow progressive nephropathy.

    wilms tumor gene 1 (WT1) is essential for normal urogenital development. Mutations in WT1 are involved in Wilms tumorigenesis and several associated syndromes, such as Denys-Drash, Frasier, or wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome. We report a novel familial WT1 point mutation in the stop codon of exon 10 (1730A/G; X450W) in 3 members of 1 family. The index patient is a 22-year-old woman in whom wilms tumor and ureter duplex were diagnosed at the age of 9 years and who subsequently developed slow progressive nephropathy. Her mother also had late-onset nephropathy that led to end-stage renal failure, whereas renal function in 1 brother of the index patient was not impaired. We hypothesize that this type of mutation (read-through), which leads to an elongated, but otherwise unchanged, WT1 protein, may be associated with incomplete penetrance and a relatively late onset of both wilms tumor and nephropathy in this family.
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ranking = 1
keywords = tumorigenesis
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