Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children with the Beckwith-Wiedemann syndrome have a greatly increased potential for the specific development of the embryonal tumours hepatoblastoma, rhabdomyosarcoma and Wilms' tumour. Data obtained with molecular probes suggest that the association between these disparate, rare tumour types reflects a common pathogenetic mechanism that entails the somatic development of homozygosity for a mutant allele at a locus on human chromosome 11.
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PMID:Loss of heterozygosity in three embryonal tumours suggests a common pathogenetic mechanism. 299 66

About 5% of Mendelian mutations displaying neoplastic tendencies are associated with chromosomal aberrations. The best established examples are retinoblastoma and del(13)(q14) and aniridia-Wilms' tumor and del(11)(p13). Evidence suggests that both mutations behave as dominant traits in the individual and as recessive traits in the cells. DNA analysis indicates that tumorigenesis arises from homozygosisty for the mutant allele at these loci, as a consequence of mitotic nondisjunction or from a mitotic recombination event. An additional argument for this conclusion is provided by the demonstration of duplication of 11p15 in some patients with the Beckwith-Wiedemann syndrome, which is complicated often by Wilms' tumor and other embryonal tumors. Data obtained with molecular probes have shown that also rhabdomyosarcoma and hepatoblastoma arise by homozygosity for a mutant allele at a locus on 11p, suggesting ontogenic relatedness of these tumor types. Additional examples of Mendelian mutations associated with chromosome deletions and neoplasia include Langer-Giedion syndrome with multiple exostoses and del(8)(q24.1), multiple endocrine neoplasia and del(20)(p12.2). While the presence of specific chromosome changes in subjects with high susceptibility to neoplasia does pinpoint the location of DNA sequences involved in the predisposition to certain types of cancers, selected Mendelian mutations associated with chromosome instability and cancer proneness may elucidate biological principles of cell proliferation and transformation. However, our current knowledge of mechanisms resulting in increased frequency of chromosome breakage and cancer susceptibility in ataxia-teleangiectasia, Fanconi's anemia, Bloom's syndrome, and similar conditions are still very incomplete.
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PMID:Cytogenetics of Mendelian mutations associated with cancer proneness. 382 76

Children with Beckwith-Wiedemann syndrome (BWS) have an increased risk of developing Wilms' tumors, hepatoblastomas, and adrenal tumors. This study evaluates disease-free survival in children with BWS and intraabdominal tumors. Sixteen tumors occurred in 13 children with BWS (8 boys, 5 girls). Diagnoses included Wilms' tumor (10) (2 bilateral, 20%), hepatoblastoma (2), bladder rhabdomyosarcoma (1), and adrenal cortical tumor (1). In the 10 children with Wilms' tumor, the average age at diagnosis was 3.5 years (range, 7 months to 5 years). Nine of 10 had initial tumor resection, chemotherapy, and radiation therapy (when indicated). One child with bilateral disease had tumor biopsy, chemotherapy, and partial nephrectomy. Tumors were classified as stage I (5), stage II (2), stage IV (1) and stage V (2), all with favorable histology. Disease-free survival rate was 100% with median follow-up of 9 years (range, 4 to 22 years). One patient had a left adrenal tumor detected during screening sonography 11 years after Wilms' tumor resection. Two infants with advanced-stage hepatoblastoma responded to chemotherapy, allowing subsequent complete hepatic resection. Both tumors had unfavorable histology. Both completed postoperative chemotherapy and have no evidence of disease (NED) with normal alpha-fetoprotein levels at 21 and 12 months, respectively, after tumor detection. One patient with stage III (group 3) bladder rhabdomyosarcoma underwent partial cystectomy following chemoradiation and is alive (NED) after 20 months. Children with BWS should be screened at regular intervals (every 3 to 6 months) for renal, adrenal, and hepatic tumors. The exact duration of screening is not yet determined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Favorable outcome in children with Beckwith-Wiedemann syndrome and intraabdominal malignant tumors. 747 29

p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation. The gene encoding human p57KIP is located on chromosome 11p15.5 (ref. 2), a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a familial cancer syndrome, marking it a tumour suppressor candidate. Several types of childhood tumours including Wilm's tumour, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the Beckwith-Wiedemann syndrome has indicated maternal carriers as well as suggested a role in genomic imprinting. Here, as a first step towards elucidating the genesis of human cancers in this region, we showed that a mouse homologue of p57KIP2 is genomically imprinted. The paternally inherited allele is transcriptionally repressed and methylated. This murine gene maps to the distal region of chromosome 7, within a cluster of imprinted genes, including insulin-2, insulin-like growth factor-2, H19 and Mash2 (refs 14-18).
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PMID:Genomic imprinting of p57KIP2, a cyclin-dependent kinase inhibitor, in mouse. 755 Mar 51

Beckwith-Wiedemann syndrome, familial atypical multiple mole melanoma syndrome, and hereditary tylosis are bona fide genodermatoses with malignant potential. Each of these conditions is associated with an increased incidence of certain tumors: Wilms' tumor, adrenocortical carcinomas, pancreatoblastomas, and hepatoblastomas in Beckwith-Wiedemann syndrome; intraocular malignant melanoma, pancreatic carcinoma, and noncolorectal gastrointestinal cancers in familial atypical multiple mole melanoma syndrome; and squamous cell carcinoma of the esophagus in hereditary tylosis. Other cancer-related genodermatoses are Birt-Hogg-Dube syndrome (associated with medullary carcinoma of the thyroid and renal cell carcinoma) and its variant, Hornstein-Knickenberg syndrome (associated with colon carcinoma). Kidney tumors (Wilms' tumor and malignant rhabdoid tumor), leukemias (acute myelogenous and acute myelomonocytic), retinoblastoma, and paratesticular rhabdomyosarcoma have been reported recently in children with another genodermatosis-incontinentia pigmenti. Supernumerary nipples (polythelia) may be sporadic or familial in occurrence; their presence has been associated with an increased incidence of renal adenocarcinoma, testicular cancer, prostate cancer, and urinary bladder carcinoma. The general characteristics, mucosal and skin manifestations, and noncutaneous features of all these conditions are reviewed. Also, the associated malignancies of these genodermatoses and other conditions that are characterized by dermatologic manifestations and may be either familial or secondary to an inherited gene defect are summarized.
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PMID:Miscellaneous genodermatoses: Beckwith-Wiedemann syndrome, Birt-Hogg-Dube syndrome, familial atypical multiple mole melanoma syndrome, hereditary tylosis, incontinentia pigmenti, and supernumerary nipples. 771 45

Insulin-like growth factor II (IGF-II) is a mitogen for many cell types and an important modulator of muscle growth and differentiation. IGF-II gene is prevalently expressed during prenatal development and its gene activity is regulated by genomic imprinting, in that the allele inherited from the father is active and the allele inherited from the mother is inactive in most normal tissues. IGF-II expression is activated in several types of human neoplasms and an alteration of IGF-II imprinting has been described in Beckwith-Wiedemann syndrome and Wilms' tumor. Here we show that monoallelic expression of IGF-II gene is conserved in normal adult muscle tissue whereas two or more copies of active IGF-II alleles, arising by either relaxation of imprinting or duplication of the active allele, are found in 9 out of 11 (82%) rhabdomyosarcomas retaining heterozygosity at 11p15, regardless of the histological subtype. Since IGF-II has been indicated as an autocrine growth factor for rhabdomyosarcoma cells, these findings strongly suggest that acquisition of a double dosage of active IGF-II gene is an important step for the initiation or progression of rhabdomyosarcoma tumorigenesis. Among different types of muscle tumors, relaxation of imprinting seems to arise prevalently in rhabdomyosarcomas, since we have detected only one case of partial reactivation of the maternal IGF-II allele out of 7 leiomyosarcomas tested.
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PMID:Mono- and bi-allelic expression of insulin-like growth factor II gene in human muscle tumors. 798 80

Imprinted genes mediate unique maternal or paternal genetic roles and their function is essential in prenatal development. The reciprocally imprinted human insulin-like growth factor 2 (IGF2) and H19 genes are expressed during embryonal life, also in the placenta, and are downregulated postnatally. They reexpress in pediatric tumors (e.g. Wilms' tumor) and in inborn developmental syndromes predisposing to such tumors (e.g., Beckwith-Wiedemann syndrome). H19 (RNA transcripts) and IGF2 are manifested in Wilms' tumor, rhabdomyosarcoma, immature ovarian teratoma and gestational trophoblastic diseases. We have found that in the placenta and in urothelial carcinoma, H19 expression reflects the degree of invasiveness. These genes, displaying a tissue-specific oncofetal pattern of expression, are, therefore, tumor markers.
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PMID:Human imprinted genes as oncodevelopmental markers. 807 25

We described a patient with Beckwith-Wiedemann syndrome associated with rhabdomyosarcoma (RMS), and renal cell carcinoma (RCC). Karyotypes of peripheral lymphocytes and RMS cells were normal. DNA analyses showed maternal loss of heterozygosity (LOH) at 11p15 region in RMS but not in RCC. The insulin-like growth factor II gene (IGF2) was found to be expressed at a moderate level in RMS but not in RCC by in situ hybridization. Each of parental allele-derived IGF2 transcript was detected in RCC, while maternal allele-derived transcript was weak in RMS because of maternal LOH. These results suggest that (1) loss of imprinting (LOI) of IGF2 might be responsible for BWS, (2) on the other hand, LOI itself might not induce tumor occurrence in tissues where the control of tissue-specific expression of IGF2 is maintained, (3) increased expression of IGF2 due to maternal loss of a putative controller gene for IGF2 at 11p15 might predispose to sustaining tumorigenic mutations and tumor progression, (4) loss of a putative onco-suppressor gene at 11p15 might induce RMS occurrence. The cause of RCC was thought to be different from that of RMS.
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PMID:Molecular analysis of a patient with Beckwith-Wiedemann syndrome, rhabdomyosarcoma and renal cell carcinoma. 808 40

Malignant rhabdoid tumors are extremely aggressive soft-tissue sarcomas that tend to be widely metastatic at diagnosis. These tumors were first described as variants of the kidney neoplasm Wilms' tumor, although tumors of similar clinicopathologic features have been cited in a variety of extrarenal sites. Here, we have characterized the chromosomal translocation t(11;22)(p15.5;q11.23) from a retroperitoneal rhabdoid tumor. Somatic cell hybrids with segregated copies of the derivative 11 and derivative 22 chromosomes allowed sublocalization of the chromosome 11 breakpoint to a 1- to 2-Mb region between the proximal marker D11S12 and the distal locus tyrosine hydroxylase (TH). Translocation-associated aberrant fragments were identified by pulsed-field gel electrophoresis, with the smallest resulting from BssHII digestion as detected with a probe for TH. These data indicate that the locus or loci disrupted by this genetic abnormality might lie less than 60 kb proximal to this marker and place it in the chromosomal vicinity of genes involved in the etiologies of rhabdomyosarcoma, Wilms' tumor, and the congenital overgrowth disorder, Beckwith-Wiedemann syndrome. Analysis of two other tumor-associated loci, EWS1 and NF2, that have been mapped to the general region of 22q11.2 indicated that they were not involved in this translocation breakpoint. Isolation of the genes present at this translocation junction on both chromosomes 11 and 22 may yield important clinicopathologic and genetic markers for this enigmatic tumor as well as other pediatric diseases.
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PMID:Molecular sublocalization and characterization of the 11;22 translocation breakpoint in a malignant rhabdoid tumor. 818 85

We report the case of a patient with Beckwith-Wiedemann syndrome (BWS) who developed renal cell carcinoma (RCC). At birth, this patient presented with macroglossia, diastasis recti, mild gigantism, hepatomegaly and hypoglycemia, and the diagnosis of BWS was made. At 22 months, an intrapelvic rhabdomyosarcoma was detected and resected. At 37 months, computed tomography (CT) demonstrated a small mass with high attenuation in the right kidney, which was surgically confirmed to be RCC.
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PMID:Renal cell carcinoma in a patient with Beckwith-Wiedemann syndrome. 865 57


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