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)

11p15.5 is an important tumor-suppressor gene region, showing loss of heterozygosity in Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. We previously mapped directly by genetic complementation a subtransferable fragment (STF) harboring an embryonal tumor-suppressor gene and spanning about 2.5 Mb. We have now mapped the centromeric end of this STF between D11S988 and D11S12 and its telomeric end between D11S1318 and TH. We have isolated a complete contig of PAC, P1, BAC, and cosmid genomic clones spanning the entire 2.5-Mb region defined by this STF, as well as more than 200 exons from these genomic clones using exon trapping. We have isolated genes in this region by directly screening DNA libraries as well as by database searching for ESTs. Nine of these genes have been reported previously by us and by others. However, the initial mapping of most of those genes was based on FISH or somatic cell hybrid analysis, and here we precisely define their physical location. These genes include RRM1, GOK (D11S4896E), Nup98, CARS, hNAP2 (NAP1L4), p57KIP2 (CDKN1C), KVLQT1 (KCNA9), TAPA-1, and ASCL2. In addition, we have identified several novel genes in this region, three of which, termed TSSC1, TSSC2, and TSSC3, are reported here. TSSC1 shows homology to Rb-associated protein p48 and chromatin assembly factor CAF1, and it is located between GOK and Nup98. TSSC2 is homologous to Caenorhabditis elegans beta-mannosyl transferase, and it lies between Nup98 and CARS. TSSC3 shows homology to mouse TDAG51, which is implicated in FasL-mediated apoptosis, and it is located between hNAP2 and p57KIP2. Thus, these genes may play a role in malignancies that involve this region.
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PMID:A 2.5-Mb transcript map of a tumor-suppressing subchromosomal transferable fragment from 11p15.5, and isolation and sequence analysis of three novel genes. 940 53

Sporadic childhood tumors associated with Beckwith-Wiedemann syndrome (BWS) all show abnormalities of the same region on chromosome 11. In addition to chromosome 11, other chromosome regions are affected in some of these tumor types. In this study we analyzed the region on chromosome 1p involved in the etiology of BWS-associated tumors, Wilms tumor, rhabdomyosarcoma, and hepatoblastoma. For this purpose we determined the location of two novel translocation breakpoints in this chromosome region in cells from a Wilms tumor and cells from a rhabdomyosarcoma. We constructed a map of the region and found that both breakpoints are separated by at least 875 kb. We identified a PAC clone which crosses the rhabdomyosarcoma breakpoint and found several exons within this clone. We established that this breakpoint is located proximal to the PAX7 gene and, therefore, identified a new region involved in the etiology of rhabdomyosarcomas.
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PMID:Delineation and physical separation of novel translocation breakpoints on chromosome 1p in two genetically closely associated childhood tumors. 1082 13

The human genome contains hundreds of repeats of the 3.3 kb family in regions associated with heterochromatin. We have previously isolated a 3.3 kb-like cDNA encoding a double homeodomain protein (DUX1). Demonstration that the protein was expressed in human rhabdomyosarcoma TE671 cells, and characterization of a homologous promoter suggested that functional DUX genes might be present in 3.3 kb elements. In the present study, we describe two nearly identical 3.3 kb/DUX genes derived from PAC 137F16 (DUX3), and TE671 genomic DNA (DUX5), both mapping to all the acrocentric chromosomes. Their promoters harbor a GC and a TATAA box, and the open reading frame of the intronless structural part encodes two DUX proteins differing by alternative translation initiation. The shorter protein of the DUX5 gene is identical to DUX1. Using a protein truncation test, we could show that these two proteins are encoded by total RNA, but not by poly (A)(+) RNA, from different human tissues and cell lines. Our results indicate that active genes of unusual structure are present in chromosome regions characterized by large amounts of heterochromatic repetitive DNA.
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PMID:Active genes in junk DNA? Characterization of DUX genes embedded within 3.3 kb repeated elements. 1124 78

The epidemiological features of rhabdomyosarcoma (RMS), an uncommon malignancy composed of cells with histopathologic features of striated muscle, were studied in Pakistan. Incident RMS cases recorded at the Karachi Cancer Registry during 1998 to 2004 were reviewed and to ensure maximum completeness of data, only those registered between 1998 and 2002 were considered for the present study. Two hundred and seventeen cases were reported to the Karachi Cancer Registry during this five-year period. One hundred and forty eight of the patients (60.4% males; 39.6% females) were residents of Karachi. The crude and standardized annual incidence rates/100,000 were 0.3 for males and 0.2 for females. The incidence was 0.5 in children below 15 years of age. The primary RMS sites in males were head and neck (28.1%), extremities (25.8%), genitourinary (GU) tract (17.9%), trunk (9.0%), orbit (7.9%), and retroperitoneum (3.4%). RMS occurred at other sites in 7.9% of the patients. Corresponding frequencies in females were head and neck (35.6%), extremities (16.9%), GU tract (16.9%), trunk (8.5%), orbit (8.5%) and other sites in 13.6%. Approximately 60% of the cases were childhood RMS and three fourths were below 21 years. The mean age of RMS cases all sites, males, was 18.5 years (95% CI 15.6; 21.4); for childhood RMS, 7.5 years (95% CI 6.0; 9.2); and for adult RMS 34.2 years (95% CI 28.3;40.2). In females, the corresponding figures were 18.2 (95% CI 13.7; 22.7); 6.6 (95% CI 5.0; 8.1) and 33.9 (95% CI 27.5; 40.5), respectively. One hundred cases were retraceable, and the mean survival time, RMS all sites and ages in both genders, was 1.5 years (95% CI 1.1; 1.9). The 5-year survival was 10%, and 3-year survival was 30% whereas 16.7% of the patients died within a year of diagnosis. The indicators of poor prognosis, a late presentation, rapid evolution, advanced disease, tumor burden (tumor size >5.cms) and regional lymph node involvement, are characteristic of RMS in Karachi. Recent advances in RMS multimodality treatment protocols have improved RMS prognosis in patients with limited disease. Pakistan should focus on early diagnosis and prompt treatment of malignancies. This requires health education for the general population to create awareness and training of health professionals at all levels to promote early diagnosis. An RMS group is required, which would monitor the treatment, recurrence, patient education and provide psychosocial support. Cytogenetic studies are advised for a better understanding of biologic differences in RMS cases in this population.
Asian Pac J Cancer Prev
PMID:Rhabdomyosarcoma in Karachi 1998-2002. 1537 8

The rhabdomyosarcoma (RMS) is the most common type of soft tissue tumor in children and adolescents; yet only a few screens for oncogenic mutations have been conducted for RMS. To identify novel mutations and potential therapeutic targets, we conducted a high-throughput Sequenom mass spectrometry-based analysis of 238 known mutations in 19 oncogenes in 17 primary formalin-fixed paraffin-embedded RMS tissue samples and two RMS cell lines. Mutations were detected in 31.6% (6 of 19) of the RMS specimens. Specifically, mutations in the NRAS gene were found in 27.3% (3 of 11) of embryonal RMS cases, while mutations in NRAS, HRAS, and PIK3CA genes were identified in 37.5% (3 of 8) of alveolar RMS (ARMS) cases; moreover, PIK3CA mutations were found in 25% (2 of 8) of ARMS specimens. The results demonstrate that tumor profiling in archival tissue samples is a useful tool for identifying diagnostic markers and potential therapeutic targets and suggests that these HRAS/ PIK3CA mutations play a critical role in the genesis of RMS.
Asian Pac J Cancer Prev 2014
PMID:Compound HRAS/PIK3CA mutations in Chinese patients with alveolar rhabdomyosarcomas. 2464 7