SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Dramatic improvements have occurred in the treatment and prognosis of the child with rhabdomyosarcoma over the past 2 decades. Increased understanding of tumor behavior has improved survival and focused attention on important quality of life issues. Future therapeutic advances will depend largely on an improved molecular understanding of altered cell behavior and the continued efforts of multi-institutional studies.
Eighteen patients with parameningeal rhabdomyosarcoma (RMS) involving the orbit were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between July 1971 and October 1983. Fifteen patients were children with a mean age of 6 years and three patients were adults with a mean age of 21 years. In four patients, the primary tumor originated in the orbit, while the remaining 14 had other parameningeal primary sites. The tumors were in a very progressive local stage, with destruction of facial bones in most patients. Six patients were treated with the T2 chemotherapy protocol and 12 received the T6 protocol. The radiation treatment plan for all patients was designed to deliver between 4500 and 7200 rad delivered to the primary tumor over 4 to 16 weeks. Eleven of the 18 patients (61%) are alive and well with a median follow-up time of six years. Two patients died of therapeutic complications and five died of tumor spread with central nervous system involvement. Ocular complications included acute and chronic conjunctival, corneal, lens, and retinal changes, which were less severe than those reported in previous series.
We describe a case of botryoid rhabdomyosarcoma with the karyotype 53,XX,+2,+5,+8,+12,+13, i(17)(q10),+19,+20. Only two cytogenetically analyzed cases of this tumor were previously reported and structural chromosomal abnormalities in each tumor were different.
The cytogenetic analysis of a spindle-cell variant of embryonal rhabdomyosarcoma (RMS), presenting as a cheek mass in an 18-year-old girl, is reported. The tumor cells showed an abnormal karyotype 46,XX,der(2)t(2;7)(q36 approximately q37;q3?),del(14)(q24),der(16)t(1;16)(q21;q13), with a tetraploid range of chromosome number in a subpopulation of cells. By fluorescence in situ hybridization analysis, the tumor cells were negative for FKHR-disrupting translocations specific for alveolar type of RMS and for NMYC gene amplification.
Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Histologically, it is subdivided histologically into two main subtypes: alveolar (ARMS) and embryonal (ERMS). ARMS is characterized by t(2;13)(q35;q14) or its variant t(1;13)(p36;q14), which fuse PAX3 and PAX7, respectively, with FKHR to produce chimeric genes. ERMS is frequently associated with loss of heterozygosity of 11p15.5. We investigated seven RMS (three ARMS and four ERMS) by means of cytogenetic, fluorescence in situ hybridization, and molecular analyses, including the study of the main genes implicated in the G1- to S-phase cell cycle transition, and correlated these studies with pathologic findings and clinical outcome. All tumors showed clonal, numerical, and structural chromosomal abnormalities. Two ARMS had the t(2;13)(q35;q14) and the third a PAX7/FKHR fusion, a cryptic t(1;13)(p36;q14), undetected by cytogenetic techniques, but revealed by reverse transcriptase polymerase chain reaction. One ERMS showed a der(11)t(3;11)(p21;p15) as a sole structural anomaly. Gene amplification was seen in four tumors, as double minutes or in the form of homogeneously staining regions. Overexpression of MYCN oncogene was found in two ARMS; N-myc DNA probe detected oncogene amplification located on the double minutes of these cases. Analysis of the regulatory genes responsible for G1- to S-phase transition showed a homozygous deletion of the 9p21 locus genes in a spindle-cell ERMS.
Alveolar rhabdomyosarcomas (ARMS) are soft-tissue tumors that are genetically characterized by the presence of reciprocal translocations that generate the fusion gene PAX3-FOXO1A or PAX7-FOXO1A. For the study of the biologic consequences of such rearrangements, several cell lines have been generated. However, established cell lines accumulate chromosome and genetic aberrations that make it difficult to draw significant conclusions. We have applied a set of techniques that includes spectral karyotyping, fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), and microarray CGH, to the most commonly used cell lines carrying the two fusion genes that are present in ARMS. We have identified the bacterial artificial chromosomes that cover the breakpoints at genes PAX3, PAX7, and FOXO1A, which can be used as FISH probes for the translocations. The RH30 cell line, positive for the PAX3-FOXO1A fusion gene, was found to be highly complex: wide range of chromosome number, more than 50 chromosome rearrangements, amplification of the hybrid gene, 24 DNA changes detected by conventional CGH, and 21 gene copy changes detected by microarray CGH (including several high-level amplifications). RMZ-RC2 cell line, positive for the PAX7-FOXO1A, was in the near-tetraploid range with only nonclonal structural rearrangements, amplification of the hybrid gene, 24 DNA changes by CGH, and 8 gene copy changes, confirming the previously reported high-level amplification of MYCN.
Cytogenetic analysis performed on a 14-month-old boy with a primary retroperitoneal/paraspinal alveolar rhabdomyosarcoma showed the presence of a der(13)t(1;13)(q23;q32) resulting in partial trisomy of the 1q23-->qter region and loss of the 13q32-->qter region. The present case is discussed with reference to a similar case reported in the literature.
Pancytopenia and fulminant disseminated intravascular coagulation in a 68-year-old woman suggested an acute hematologic malignancy. However, cytogenetic analysis on a bone marrow sample revealed a near-tetraploid karyotype with an isochromosome 1q and a translocation (2;13) (q35;q14), which was suggestive of an alveolar rhabdomyosarcoma (ARMS). This diagnosis was subsequently confirmed by indirect immunohistochemistry. ARMS has not yet been observed in a patient of this age. Thus, our case underlines the importance of cytogenetics, to establish an a priori unexpected tumor diagnosis.
The cytogenetic analysis of a spindle-cell rhabdomyosarcoma of the parotid gland in a 6-year-old boy is reported. The tumor cells showed an abnormal karyotype with a hypotriploid modal chromosome number and clonal structural rearrangements affecting chromosomes 1, 8, 12, 21, and 22. The tumor karyotype was: 59, XY, -1, -3, -4, -5, -6, +8, +8, +del(8)(q22q24), -9, -10, del(12)(q13), -15, -16, -17, -18, der(21)t(12;21)(p11;p11), -22, der(22)t(1;22)(q12;p11).
An embryonal rhabdomyosarcoma, presenting as a retroperitoneal mass in a 15-year-old girl, is reported. The histological and immunohistochemical picture was typical, except for the presence of focal chondroid differentiation. Interestingly, expression of the "muscle markers" desmin and alpha-sarcomeric actin was present in the latter areas. Cytogenetic analysis showed a hyperdiploid karyotype without structural chromosome changes. The pertinent literature on the subject is reviewed. Hyperdiploidy of the clonal type seems to occur frequently, but no characteristic karyotype is so far emerging.
In the pediatric cancer alveolar rhabdomyosarcoma, the common 2;13 and less frequent 1;13 translocations fuse PAX3 and PAX7, respectively, with FKHR to produce chimeric genes. To compare structural features of these rearrangements, we cloned and mapped a 64-kb genomic region containing PAX7 exons 5 through 8. With the use of Southern blot methodology, rearrangements of the 30-kb PAX7 intron 7 were detected in 9 of 9 PAX7-FKHR-positive cases. Similar to our t(2;13) studies, the t(1;13) breakpoints were randomly distributed within the seventh intron. In contrast with the > 90% frequency of reciprocal rearrangements in the t(2;13), reciprocal rearrangements involving the 3' PAX7 region were detected in only 4 of 9 cases. Furthermore, we detected PAX7-FKHR genomic amplification in 10 of 11 cases, in contrast with the < 5% frequency of PAX3-FKHR amplification. The differences in occurrence, reciprocity, and amplification between the PAX3-FKHR and PAX7-FKHR fusions indicate important differences in the mechanism of the two associated chromosomal translocation events.
This therapeutic trial deals with 81 patients with stage III rhabdomyosarcoma (RMS), from different centers of the International Society of Pediatric Oncology. These patients were included between October 1975 and March 1983. The aim of this work is to minimize the sequelae of treatment without jeopardizing the survival rate. After a pretrial course of VAC, two groups of patients are compared: the first treated with systematic extensive surgery or radiotherapy on the initial tumor volume, and the second treated with combined chemotherapy using vincristine, dactinomycin, adriamycin, cyclophosphamide until maximum tumor reduction, followed by radiotherapy or surgery on the residual mass only. Eighty one patients were included in the trail; 15 patients were not randomized due to the failure of the pretrial course of chemotherapy, 3 were excluded after randomization (2 were found not to have RMS, and in one case the protocol was not observed). The preliminary results for the 63 patients show a survival rate of 40% at 3 years. The sequential scheme for patients at 3 years follow-up does not show a superiority in either arm.
The effect of graded external radiation doses and a dose administered by an implanted 125I seed on growth delay and cure rate of a rat rhabdomyosarcoma was investigated. One 125I seed (0.40 or 0.50 mCi) was implanted per tumour when the tumours had grown to a predetermined size. The irradiation by the 125I seed did not cause significant tumour growth delay. When implantation of an 125I seed was combined with graded external radiation doses, the growth delay observed after these combined regimens was significantly greater than that observed after treatment with external doses alone. The same was observed for tumour cure rates. The effectiveness of the 125I seed could be assessed as being equivalent to a single dose of external radiation of about 6-20 Gy, depending on the external dose applied. The application of 125I seeds combined with external irradiation to obtain local control might be recommended in those cases where the total dose of external radiation alone is limited by normal tissue reactions.
We describe a patient with rhabdomyosarcoma of the posterior cervical region and clear cell sarcoma on the occipital scalp. These two tumors later metastasized to distant skin. We differentiated these tumors by histopathologic, histochemical, immunohistochemical, and ultrastructural findings. Cells of the posterior cervical tumor showed differentiation toward striated muscle, whereas those of the occipital tumor showed findings compatible with melanocytic differentiation.
Expression of determined Asn-bound glycans (N-glycans) in cell surface glycoproteins regulates different processes in tumour cell biology. Specific patterns of N-glycosylation are displayed by highly metastatic cells and it has been shown that inhibition of N-glycan processing restrains cell proliferation and induces cell death via apoptosis. However, the mechanisms by which different N-glycosylation states may regulate cell viability and growth are not understood. Since malignant cells express high levels of intracellular glutathione (GSH) and a reduction of intracellular GSH induces cell death via apoptosis, we investigated whether GSH was involved in the induction of apoptosis by removal of cell surface N-glycans. We found that removal of N-glycans from cell surface proteins by treating the rhabdomyosarcoma cell line S4MH with tunicamycin or N-glycosidase resulted in a reduction in intracellular GSH content and cell death via apoptosis. Moreover, GSH depletion caused by the specific inhibitor of GSH synthesis BSO induced apoptosis in S4MH cells. This data indicates that adequate N-glycosylation of cell surface glycoproteins is required for maintenance of intracellular GSH levels that are necessary for cell survival and proliferation.
The most common signs of a malignancy in the region of the head and neck are evidence of a mass or symptoms arising from it. In this report a patient is described with rhabdomyosarcoma of the mandible. An incidental x-ray taken some 3 months prior to the onset of clinical symptoms showed no evidence of bone involvement of the mandible. The onset of bone destruction of the angle and ascending ramus of the mandible as seen on a subsequent x-ray can be placed somewhere in this period of time.
Five primary and two metastatic rhabdomyosarcomas (RMS) with primary presentation in the skin were studied by conventional light microscopy and immunohistochemistry. These cases account for only 0.7% of the 682 cases of RMS collected at two large institutions with a main interest in soft tissue tumors. All but one tumor, which was an embryonal RMS, corresponded to the alveolar subtype. The myogenic nature of the tumor cells was supported by the immunophenotype including positive reactions for vimentin, desmin, and muscle actin. Clinical findings included a male predominance, young age of the patients and the location of all primary cutaneous RMS in the face. One of the two metastatic RMS presented at birth with a clinical picture highly suggestive of congenital metastatic neuroblastoma, notably because of a 100-fold amplification of the N-myc copy number. Thus, this case illustrates again that an amplification of the N-myc oncogene is not restricted to neuroblastoma, but may also occur in other tumor types.
We describe an unusual case of a rhabdomyosarcoma (RMS) in that it had rhabdoid-like cells histologically and occurred in a female who had undergone bone marrow transplantation for chronic myelogenous leukemia. The tumor was composed of loosely cohesive cells with abundant eosinophilic cytoplasm and exhibited PAS-negative paranuclear inclusions. The tumor cells had positive vimentin, muscle-specific actin, sarcomeric actin and desmin immunoreactivity. Ultrastructurally, the tumor cells contained aggregates of thin and thick filaments. In situ hybridization did not detect human papillomavirus or cytomegalovirus DNA, or EBV DNA or RNA. The tumor fulfilled the current criteria for a diagnosis of RMS; however, it could not be further classified. The tumor appears to have a good prognosis as there has been no evidence of recurrence five years after resection. As this is the first case report, to our knowledge, of this type of tumor following bone marrow transplant, the significance of this association is not yet clear.