Rhabdomyosarcomas (RMS) constitute a heterogeneous spectrum of tumors with respect to clinical behavior and tumor morphology. The paternal uniparental disomy (pUPD) of 11p15.5 is a molecular change described mainly in embryonal RMS. In addition to LOH, UPD, the MLPA technique (ME030kit) also determines copy number variants and methylation of H19 and KCNQ1OT1 genes, which have not been systematically investigated in RMS. All 127 RMS tumors were divided by histology and PAX status into four groups, pleomorphic histology (n = 2); alveolar RMS PAX fusion-positive (PAX+; n = 39); embryonal RMS (n = 70) and fusion-negative RMS with alveolar pattern (PAX-RMS-AP; n = 16). The following changes were detected; negative (n = 21), pUPD (n = 75), gain of paternal allele (n = 9), loss of maternal allele (n = 9), hypermethylation of H19 (n = 6), hypomethylation of KCNQ1OT1 (n = 6), and deletion of CDKN1C (n = 1). We have shown no difference in the frequency of pUPD 11p15.5 in all groups. Thus, we have proven that changes in the 11p15.5 are not only specific to the embryonal RMS (ERMS), but are often also present in alveolar RMS (ARMS). We have found changes that have not yet been described in RMS. We also demonstrated new potential diagnostic markers for ERMS (paternal duplication and UPD of whole chromosome 11) and for ARMS PAX+ (hypomethylation KCNQ1OT1).

• MeSH
• alveolární rhabdomyosarkom * genetika   MeSH
• chromozomy MeSH
• embryonální rhabdomyosarkom * genetika   patologie   MeSH
• lidé MeSH
• metylace DNA MeSH
• rhabdomyosarkom * genetika   MeSH
• uniparentální disomie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Rhabdomyosarcomas (RMS) are a heterogeneous group of mesodermal tumors, the most common sub-types are embryonal (eRMS) and alveolar (aRMS) rhabdomyosarcoma. Immunohistochemical analysis revealed c-Myb expression in both eRMS and aRMS. c-Myb has been reported to be often associated with malignant human cancers. We therefore investigated the c-Myb role in RMS using cellular models of RMS. Specific suppression of c-Myb by a lentiviral vector expressing doxycycline (Dox)-inducible c-Myb shRNA inhibited proliferation, colony formation, and migration of the eRMS cell line (RD), but not of the aRMS cell line (RH30). Upon c-Myb knockdown in eRMS cells, cells accumulated in G0/G1 phase, the invasive behaviour of cells was repressed, and elevated levels of myosin heavy chain, marker of muscle differentiation, was detected. Next, we used an RD-based xenograft model to investigate the role of c-Myb in eRMS tumorigenesis in vivo. We found that Dox administration did not result in efficient suppression of c-Myb in growing tumors. However, when c-Myb-deficient RD cells were implanted into SCID mice, we observed inefficient tumor grafting and attenuation of tumor growth during the initial stages of tumor expansion. The presented study suggests that c-Myb could be a therapeutic target in embryonal rhabdomyosarcoma assuming that its expression is ablated.

• MeSH
• embryonální rhabdomyosarkom genetika   metabolismus   patologie   MeSH
• G0 fáze * MeSH
• G1 fáze * MeSH
• genový knockdown MeSH
• karcinogeneze genetika   metabolismus   patologie   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• protoonkogenní proteiny c-myb genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• akutní lymfatická leukemie * genetika   MeSH
• akutní myeloidní leukemie * genetika   MeSH
• alveolární rhabdomyosarkom genetika   MeSH
• dítě MeSH
• embryonální rhabdomyosarkom genetika   MeSH
• Ewingův sarkom * MeSH
• lidé MeSH
• lymfoidní leukemie MeSH
• melanom genetika   MeSH
• mikro RNA * MeSH
• nádory centrálního nervového systému * MeSH
• organogeneze genetika   MeSH
• rhabdomyosarkom * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. There are two major histopathological types of RMS – embryonal (eRMS) and alveolar (aRMS). A molecular study of Igf2, MyoD1 and Myogenin was performed to determine the expression profiles and to assess the possible utility of these genes as potential treatment targets. Patients with RMS showed up to 100-fold increase of Igf2 transcription in comparison with normal skeletal muscle. Our data suggest that overexpression of Igf2 occurs in RMS of both histological subtypes. No correlation between the results of Igf2 mRNA expression and LOH at the 11p15 region (p= 0.12) was observed, but there was a trend of a higher expression of Igf2 mRNA in RMS samples with LOH. We observed a high level of MyoD1 mRNA in both aRMS and eRMS, and we detected a similar level of MyoD1 mRNA in RMS and normal skeletal muscles. There was a correlation between the results of MyoD1 mRNA expression and LOH at the 11p15 region.We did not observe any statistical difference in the level of Myogenin mRNA in the subgroups of RMS. Analogous to MyoD1, we observed a similar level of Myogenin mRNA in RMS and normal skeletal muscles.

• MeSH
• alveolární rhabdomyosarkom genetika   MeSH
• dospělí MeSH
• embryonální rhabdomyosarkom genetika   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• insulinu podobný růstový faktor II genetika   MeSH
• kosterní svaly metabolismus   patologie   MeSH
• kostní dřeň metabolismus   patologie   MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• míra přežití MeSH
• MyoD Protein genetika   MeSH
• myogenin genetika   MeSH
• nádorové biomarkery genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• prognóza MeSH
• transkripční faktor PAX7 genetika   MeSH
• ztráta heterozygozity MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Childhood rhabdomyosarcoma (RMS) has two major histological subtypes: alveolar (aRMS) and embryonal. The aim of the study was to monitor minimal disseminated disease (MDD) using real-time quantitative reverse-transcription PCR (RQ-RT-PCR) of the PAX3-FKHR, PAX7-FKHR fusion genes and myoD1 gene. We prepared an assay using RQ-RT-PCR for a quantitative assessment of MDD in aRMS by using hydrolysis probe for quantification of PAX3-FKHR, PAX7-FKHR and myoD1 genes and beta-2-microglobulin housekeeping gene. Primary tumor samples (44), samples of local recurrences (26) from 48 patients with aRMS were examined by nested RT-PCR and RQ-RT-PCR techniques. Additionally, bone marrow samples (115), peripheral blood progenitor cell samples (27), and peripheral blood samples (25) from 33 aRMS patients were tested. PAX3/7-FKHR and myoD1 transcripts proved to be a sensitive tool for detection of MDD in RMS. We were able to identify 15/25 patients with bone marrow (BM) involvement at the time of presentation using RQ-RT-PCR. We analyzed PAX3-FKHR or PAX7-FKHR expression during the course of the disease. The RQ-RT-PCR results correlated well with nested RT-PCR results (p < 0.0001). The presence of metastases is the most adverse prognostic factor in RMS, and bone marrow is a frequent site of the tumor dissemination in RMS, especially in aRMS. Our results detecting the fusion transcripts or myoD1 transcript in the BM or peripheral blood suggest that patients with positive findings are at high risk of the tumor progression.

• MeSH
• alveolární rhabdomyosarkom chemie   genetika   patologie   MeSH
• dítě MeSH
• embryonální rhabdomyosarkom genetika   patologie   MeSH
• forkhead transkripční faktory analýza   MeSH
• kojenec MeSH
• kostní dřeň chemie   patologie   MeSH
• lidé MeSH
• lokální recidiva nádoru patologie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• MyoD Protein genetika   MeSH
• nádorové biomarkery analýza   MeSH
• polymerázová řetězová reakce s reverzní transkripcí metody   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• rekombinantní fúzní proteiny analýza   MeSH
• rhabdomyosarkom chemie   genetika   mortalita   patologie   MeSH
• transkripční faktor PAX7 analýza   MeSH
• transkripční faktory paired box analýza   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The somatic type tumors are occasionally found in nonseminomatous germ cell tumors in men. These malignancies are presumed to arise from malignant transformation (MT) of teratoma or by differentiation of totipotential germ cell. OBSERVATION: A case of MT of germ cell tumor in 17-year-old male into embryonal rhabdomyosarcoma is described. The histopathologic diagnosis was that of embryonal rhabdomyosarcoma in which no germ cell elements were found. The germ cell origin of transformed histology is supported by cytogenetic analysis (isochromosome 12p), and elevated alpha(1)-fetoprotein. Despite intensive therapy the patient died. CONCLUSIONS: MT of teratoma is rare entity with poor prognosis.

• MeSH
• chromozomální aberace MeSH
• cytogenetické vyšetření MeSH
• embryonální rhabdomyosarkom * diagnóza   genetika   terapie   MeSH
• fatální výsledek MeSH
• imunohistochemie MeSH
• lidé MeSH
• lidské chromozomy, pár 12 genetika   MeSH
• lymfatické metastázy MeSH
• mladiství MeSH
• nádorová transformace buněk * genetika   MeSH
• nádory mediastina * diagnóza   genetika   terapie   MeSH
• nádory plic * diagnóza   sekundární   MeSH
• reziduální nádor MeSH
• sekundární malignity * diagnóza   genetika   terapie   MeSH
• teratom * diagnóza   genetika   terapie   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH