1/11. Primitive neuroectodermal tumors of the biliary and gastrointestinal tracts: clinicopathologic and molecular diagnostic study of two cases.Primitive neuroectodermal tumor (PNET) is a prototypic malignant small round cell tumor of childhood that is characterized in most cases by t(11;22) resulting in an EWS-FLI1 gene fusion. Once thought to be uncommon, PNET now accounts for almost 20% of malignant soft tissue tumors in children. Increased recognition of PNET is partly due to advances in immunohistochemistry and molecular diagnostics, which have led to the identification of the tumor in non-classical sites. We report the clinical, histologic, immunohistochemical, and molecular findings of two visceral PNETs of the digestive system--one involving the small intestine and the other involving the hepatic duct. Histologically, each tumor was composed of malignant small cells growing in sheets, nests, and lobules; the tumor cells of both cases showed characteristic immunoreactivity for vimentin and O13 (CD99). reverse transcription-polymerase chain reaction (RT-PCR) analysis for t(11;22) using nested primers was performed with rna extracted from paraffin-embedded, formalin-fixed tissue and demonstrated an EWS exon 7 to FLI1 exon 5 fusion in both cases, confirmed by Southern blot hybridization and dna sequence analysis. These results illustrate the expanded clinicopathologic profile of PNET, and demonstrate that visceral PNETs, despite their unusual sites of presentation, maintain the characteristic immunohistochemical and genetic features of PNETs at more conventional sites.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/11. Detection of a novel t(6;15)(q21;q21) in a pediatric wilms tumor.We report a novel cytogenetic finding in a favorable histology wilms tumor occurring in a 4-month-old boy. Karyotypic analysis demonstrated a t(6;15)(q21;q21) in all tumor cells examined. This was confirmed using fluorescence in situ hybridization analysis. Molecular analysis of this rearrangement may provide clues to understanding the pathobiology of wilms tumor.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/11. Genetic changes of two Wilms tumors with anaplasia and a review of the literature suggesting a marker profile for therapy resistance.Cytogenetic data on Wilms tumors (WT) with anaplasia frequently associated with an unfavorable outcome are scarce. We present cytogenetic changes of two WT with anaplasia (primary tumor material) from nonresponders with a synopsis of the literature. The WT were investigated by cytogenetic analysis, comparative genomic hybridization, fluorescence in situ hybridization, immunofluorescence, and flow cytometric analyses. Both tumors exhibited characteristic genetic changes. One tumor was hypodiploid due to loss of entire chromosome 11; losses of 16p, 16q, 17p, chromosome 19 material, and loss of 22q12-qter. The other tumor was hyperdiploid and triploid, and displayed gain of 1q12-q23 and chromosome 9 material. Moreover, two morphological and genetically distinct cell lines have been established from both tumors, demonstrating underrepresentation of chromosomes 13, 14, 16, and 19. karyotype descriptions of 120 WT with known clinical data together with data of this report confirm: (1) inter- and intratumor heterogeneity exists; (2) loss or underrepresentation of chromosome material at 11, 13, 14, 16, 17p, 19, and 22q in various combinations presents a new marker profile of resistance to cytotoxic agents regardless of the histological types; and (3) the prognostic impact of gain at 1q12-q23 sequences warrants further validation.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
4/11. Constitutional partial 1q trisomy mosaicism and wilms tumor.We report on a female patient with severe-profound mental retardation, multiple congenital anomalies, as well as a history of mosaicism for partial 1q trisomy in the amniotic fluid and a previous wilms tumor specimen. Peripheral blood and fibroblasts were studied and did not demonstrate the mosaicism initially detected for 1q. Array comparative genomic hybridization yielded negative results. Additional cytogenetic studies helped clarify the previous findings and revealed evidence of partial 1q trisomy mosaicism in normal kidney tissue and in a kidney lesion. GTG-banded results showing low-percentage mosaicism for the structural rearrangement der(1)t(1;1)(p36.1;q23) in both tissues were corroborated by fluorescence in situ hybridization studies. We hypothesize that the partial 1q trisomy predisposed the target tissue (in this case kidney) to neoplasia. This study provides further support for the hypothesis that certain constitutional chromosomal abnormalities can predispose to cancer. As detection of a low-percentage mosaicism may be hampered by the limits imposed by currently available technology and the constraint of a finite sample size, extra vigilance in monitoring other somatic tissues will be needed throughout the patient's lifetime. Anticipatory clinical guidance and prognostication are meaningful only if given accurate cytogenetic diagnoses. To the best of our knowledge, this is the first reported case of wilms tumor associated with constitutional partial 1q trisomy, either in pure or mosaic form, with the particular 1q23 breakpoint in conjunction with a break on 1p36.1.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
5/11. N-myc oncogene expression in histopathologically unrelated bilateral pediatric renal tumors.Renal tumors of childhood occasionally exhibit histopathologic and clinical features that preclude accurate diagnosis. Molecular and cell culture techniques may be helpful in better characterizing these cases. This approach was used to examine unusual bilateral renal tumors from a young boy. The left kidney tumor was an undifferentiated neoplasm with light microscopic features suggestive of both Wilms' tumor and neuroblastoma, and the right kidney tumor was identified as multilocular cystic nephroma (MLCN). in vitro tissue culture of tumor cells and hybridization experiments with an N-myc oncogene dna probe contributed to a revised diagnosis of intrarenal neuroblastoma of the left kidney. A cell line established from the left tumor exhibited neurite outgrowth and was positive for neuron-specific enolase and synaptophysin. N-myc was greater than ten-fold amplified in chromosomal dna from the left kidney tumor. Measurement of N-myc rna expression enabled distinction between benign and malignant tumor tissue. The detection of N-myc gene amplification predicted a poor prognosis which was confirmed by the patient's subsequent clinical course.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/11. Localization of the oncogene c-Ha-ras1 outside the aniridia-Wilms' tumor-associated deletion of chromosome 11(del 11p13) using somatic cell hybrids.Hybrid cell lines, obtained after fusion of rodent cells with leukocytes from a patient with the aniridia-Wilms' tumor syndrome and carrying a specific constitutional deletion in chromosome #11 (del.11p13), were assayed for the presence of the c-Ha-ras1 oncogene. This sequence has recently been assigned to the p-arm of chromosome #11 and, hence, has been suggested to be involved in the development of renal tumors in patients with this syndrome. Positive hybridization of a cellular Ha-ras1 probe to hybrid cell dna was observed, irrespective of whether the normal chromosome #11 or its deleted homologue was present. The results presented here suggest that c-Ha-ras1 is located outside the region 11p12-11p14, bounded by the chromosomal breakpoints observed in the patient used. Therefore, we conclude that predisposition of aniridia patients to develop Wilms' tumors is not due to a constitutional deletion of one of the c-Ha-ras1 alleles.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/11. Origin and biology of a testicular Wilms' tumor.A pure triphasic testicular Wilms' tumor, without teratomatous elements, was studied using multiple techniques. carcinoma in situ (CIS), the characteristic precursor of testicular germ cell tumors of adults (TGCTs), was found in the adjacent parenchyma. Flow cytometric analysis showed a single hypotriploid tumor stem line. karyotyping of the tumor revealed some numerical and structural abnormalities, including an i(12p), the chromosomal marker of TGCTs. in situ hybridization supported the karyotypic findings, and showed a similar numerical distribution in CIS and the tumor. Molecular analysis of the tumor illustrated that all short arms of chromosome 12, including i(12p), were of maternal origin. No 12q deletions were detected. In spite of complete loss of the paternal 11p13 band, the zinc finger regions and exons 2 and 6 of the WT1 gene contained no aberrations. Therefore, this tumor suppressor gene is not inactivated due to aberrations in the studied regions. In addition, all four WT1 alternative transcripts were expressed in the tumor. No aberrations were found in chromosomal bands 11p15.5, 16q22.1, and 16q24. Both parental alleles of the human imprinted genes H19 and IGF2 were expressed in the tumor. This is the first report on the chromosomal and molecular characterization of an extrarenal Wilms' tumor. Its germ cell origin was unequivocally demonstrated.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/11. Pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in a family.The combined use of qualitative and quantitative analysis of 11p13 polymorphic markers together with chromosomal in situ suppression hybridization (CISS) with biotin labeled probes mapping to 11p allowed us to characterize a complex rearrangement segregating in a family. We detected a pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in the family: an insertion of brand 11p13-p14 carrying the genes for predisposition to Wilms' tumor, WT1, and for aniridia, AN2, into the long arm of chromosome 11 in 11q13-q14. Asymptomatic balanced carriers were observed over three generations. Classical cytogenetics had failed to detect this anomaly in the balanced carriers, who were first considered to be somatic mosaics for del(11)(p13). Two of these women gave birth to children carrying a deleted chromosome 11, most likely resulting from the loss of the 11p13 band inserted in 11q. Although in both cases the deletion encompassed exactly the same maternally inherited markers, there was a wide variation in clinical expression. One child, with the karyotype 46,XY, del(11)(p13p14), presented the full-blown wagr syndrome with aniridia, mental retardation, Wilms' tumor, and pseudohermaphroditism, but also had proteinuria and glomerular sclerosis reminiscent of Drash syndrome. In contrast, the other one, a girl with the karyotype 46,XX,del(11)(p13), only had aniridia. Although a specific set of mutational sites has been observed in Drash patients, these findings suggest that the loss of one copy of the WT1 gene can result in similar genital and kidney abnormalities.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/11. Localization of a novel t(1;7) translocation associated with Wilms' tumor predisposition and skeletal abnormalities.cytogenetic analysis of predisposition syndromes has played a critical role in the elucidation of the genetics of Wilms' tumor (WT). Therefore, we became interested in a patient who presented with a WT and a nephrogenic rest in the contralateral kidney (suggestive of a predisposition) and a de novo t(1;7)(q42;p15) constitutional translocation as the only visible cytogenetic abnormality. He also had bilateral radial aplasia and other skeletal abnormalities, but there was no manifestation of any syndrome previously associated with WT. In the tumor, the translocation was retained, and the other 7p region was lost by the formation of an isochromosome i(7q). Here, we report the localization of the chromosome 7 breakpoint within a yeast artificial chromosome (YAC) contig by using fluorescence in situ hybridization (FISH), localizing the breakpoint between markers sWSS355 and sWSS1449. A number of YACs span the breakpoint and, thus, contain the region that is disrupted by the translocation. This may represent the site of a novel tumor suppressor gene that is involved in WT and also in normal renal development.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/11. Renal pathology in wagr syndrome.The Wilms' tumor-aniridia-genital anomalies-mental retardation (WAGR) syndrome is associated with an increased risk for developing Wilms' tumor. A right nephrectomy was performed following the diagnosis of Wilms' tumor in a 2-year-old girl with wagr syndrome and chromosome 11, del 11p13. Pathologic examination revealed intralobar nephrogenic rests and a peripelvic multicystic mass, sharply delineated from the adjacent typical intralobar nephrogenic rests and renal parenchyma, which may represent a cystic Wilms' tumor (cystic partially differentiated nephroblastoma). We studied the expression of the H19 gene by in-situ hybridization performed on paraffin sections of the kidney. H19 is an imprinted maternally-expressed gene that is not translated to protein and functions as a regulatory rna molecule. It is tightly linked with the paternally-imprinted gene of insulin-like growth factor 2. While IGF2 presumably plays a role in tumorigenesis of Wilms' tumor, H19 is not expressed in the majority of Wilms' tumors. The expression of H19 in the intralobar nephrogenic rests was found to be prominent in the component of the blastema and markedly reduced with differentiation to tubular structures similar to the fetal kidney. The differential diagnosis of hyperplastic intralobar nephrogenic rests from a small Wilms' tumor arising in intralobar nephrogenic rests is difficult. Complete understanding of the chain of molecular events occurring in the evolution of Wilms' tumors may lead to the development of tumor markers to be used on paraffin sections and so help in the differential diagnosis of hyperplasia versus malignant transformation.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
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