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J A Bridge

Publications and source records attributed to J A Bridge.

At least 55 records · Page 3Linked to original sources
PubMed1998

Characterization of a variant SYT-SSX1 synovial sarcoma fusion transcript.

Synovial sarcoma is characterized cytogenetically by an X;18 translocation [t (X;18) (p11;q11)] that results in the fusion of the SYT gene from chromosome 18 to either of two highly homologous genes at Xp11, SSX1 or SSX2. Heterogeneity within the synovial sarcoma fusion junctions is rare. Examination of a primary monophasic synovial sarcoma for an SYT-SSX fusion transcript by reverse-transcription polymerase chain reaction revealed a smaller-than-expected product. Direct sequencing of the product disclosed a novel SYT-SSX1 fusion transcript that contained an additional 51 bp of normal SSX1 sequence but lost 135 bp of the SYT sequence. Detection of synovial sarcoma hybrid transcripts is useful for diagnosis and should include the recognition of distinct variants.

Amino Acid Sequence↗
PubMed1998

Peripheral primitive neuroectodermal tumors in adults: documentation by molecular analysis.

PURPOSE: The Ewing tumor (ET) family of peripheral primitive neuroectodermal tumors (pPNETs) are primitive small round-cell tumors (SRCTs) of the bone and soft tissue that occur predominantly in children and adolescents. However, pPNETs only rarely enter the differential diagnosis of bone and soft tissue SRCTs in adults. Recently, gene fusions between the EWS gene and different members of the ETS transcription factor family have been shown to occur in virtually all pPNETs and thus constitute a pathognomonic marker for this tumor subclass. The aim of the present study was to document EWS/ETS fusion gene expression in suspected pPNETs of adults as objective evidence for the existence of this tumor family in older patients. PATIENTS AND METHODS: The three contributing molecular diagnostic laboratories retrospectively compiled a cohort of all SRCT cases in which EWS/ETS gene fusions had been shown by molecular analysis. This cohort was surveyed for cases that occurred in patients aged 40 years or older, which were then analyzed for their clinical and pathologic features. RESULTS: Nine patients between 40 and 65 years of age were found to have tumors positive for EWS/ETS gene fusions. Standard histopathologic and clinical features of these cases, other than age, were similar to those of childhood pPNETs. Patients were initiated on appropriate therapy after molecular analysis confirmed the diagnosis of pPNET. CONCLUSION: Identification of an EWS/ETS gene fusion is useful in providing objective evidence of the diagnosis of pPNET in patients over the age of 40 years. This diagnosis should be considered in adults who present with bone and soft tissue SRCTs and appropriate biopsy specimens should be collected for molecular analysis at the time of diagnosis.

Adult↗
PubMed1998

Low-level chromosome 12 amplification in a primary lipoma of the lung: evidence for a pathogenetic relationship with common adipose tissue tumors.

Cytogenetic analysis of a primary lipoma of the lung removed from a 56-year-old woman revealed the presence of a supernumerary marker chromosome in all metaphase cells analyzed; namely, 47,XX,+mar. To the best of our knowledge, this is the first cytogenetic description of a primary lipoma of lung. Genetic analysis of intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma have revealed the presence of one to three supernumerary ring or giant marker chromosomes composed of chromosome 12 segments as the characteristic anomaly. The marker chromosome in the present case was shown to be composed entirely of chromosome 12 material by subsequent analysis with a chromosome 12-specific paint probe and fluorescence in situ hybridization. Thus, analogous to intramuscular lipoma, atypical lipoma, and well-differentiated liposarcoma, extra chromosome 12 material is present. These findings support a pathogenetic relationship between this lipoma of unusual anatomic location and common adipose tissue tumors.

Chromosome Aberrations↗
PubMed1997

Chromosomal abnormalities in low grade chondrosarcoma and a review of the literature.

In this study, cytogenetic analysis of two low-grade chondrosarcomas revealed relatively simple chromosomal complements with structural rearrangements involving chromosomes 1, 6, and 12 [46,XY,add(16)(q24)[3]/46,XY,t(1;20)(q21;q11),t(6;17)(q23;q23)[3]/46,XY, t(4;14)(q12;q24),t(5;6)(q12;p21) [2] and 45,XY,t(12;16)(q13;q24),-14[17]/44,idem,add(4)(p16),-17,[2] respectively]. Previously published reports of chondrosarcoma have revealed structural abnormalities of chromosomes 1, 6, 9, 12, and 15 as common. Also, a correlation between the simplicity or complexity of the abnormalities seen and histologic grade has been suggested. The findings of the current study support these earlier observations.

Chondrosarcoma↗
PubMed1997

Chromosomal anomalies in a case of proliferative myositis.

Proliferative myositis, a reactive lesion similar to proliferative fasciitis and nodular fasciitis, has only been cytogenetically described in one other report to date. This previously described case showed trisomy 2. Cytogenetic analysis and fluorescence in situ hybridization (FISH) of a proliferative myositis lesion in the present study did not reveal trisomy 2 but the following clonal translocation was observed: 46,XX,t(6;14)(q23;q32).

Chromosomes, Human, Pair 14↗
PubMed1997

Synovial sarcoma of the head and neck: chromosomal translation (X;18) as a diagnostic aid.

BACKGROUND: Synovial sarcoma, a rare tumor in the head and neck, has been historically diagnosed by its characteristic biphasic histologic pattern. Monophasic variants exist which can be difficult to diagnose. METHODS: Two cases of synovial sarcoma of the head and neck are presented. Both cases, cytogenetic analysis was performed using standard protocols. RESULTS: Both tumors demonstrated a chromosomal translocation, t(X;18)(p11.2;q11.2), which either made or confirmed the diagnosis. CONCLUSIONS: Synovial sarcoma contains a characteristic chromosomal translocation which is a useful diagnostic tool, especially when histologic studies are equivocal.

Adult↗
PubMed1997

Characterization of a human myxoid malignant fibrous histiocytoma cell line, OH931.

Malignant fibrous histiocytoma (MFH), the most common soft-tissue sarcoma of late adult life, includes several histopathologic subtypes. The myxoid MFH subtype is characterized by the presence of abundant mucopolysaccharide within a loose connective tissue stroma. Although the myxoid variant is typically distinguished clinically by its better prognosis, we report a case of myxoid MFH that exhibited an aggressive phenotype with early metastases and death. A cell line, OH931, was established from this myxoid MFH. The primary tumor, OH931 cell line, and cells recovered from tumors generated in nude mice shared similar morphologic features, including the continued production of abundant mucopolysaccharide. Cytogenetic analysis of the primary tumor and a subsequently established cell line (OH931) revealed a complex hypertriploid mainline. Chromosomal breakpoints involved in all three specimens analyzed (diagnostic biopsy, definitive surgical, and cell line) included 1p33, 1q21, 2p14, 4p15, 5q13, 12q13, 14p13, 15p13, 19q13 and 20q13.1. The OH931 cell line, which appears to maintain its peculiar characteristics in vitro, should be useful in studies investigating the role of mucopolysaccharide production in the process of neoplasia.

Aged↗
PubMed1997

Cytogenetic findings in 73 osteosarcoma specimens and a review of the literature.

Tumor-specific chromosomal abnormalities have been identified in several histologic subtypes of sarcomas. Characterization of recurrent chromosomal abnormalities has provided direction for molecular investigations of pathogenetically important genes. Cytogenetic reports of osteosarcoma, the most common primary malignant bone tumor, are relatively rare. In this study, 73 osteosarcoma specimens from 51 patients were cytogenetically analyzed following short-term culture. Clonal chromosomal abnormalities were detected in 47 and included one haploid specimen, 18 near-diploid specimens, 17 near-triploid, 8 near-tetraploid, 1 near-hexaploid, and 2 specimens with multiple clones of different ploidy levels. Examination of the present data and previously published data (111 clonally abnormal osteosarcoma specimens) reveals that chromosomal bands or regions 1p11-13, 1q10-12, 1q21-22, 11p15, 12p13, 17p12-13, 19q13, and 22q11-13 are most frequently rearranged and the most common numerical abnormalities are +1, -9, -10, -13, and -17. Partial or complete loss of the long arm of chromosome 6 also was seen in all cases of the present study and all previously published cases describing structural abnormalities of 6q. Parosteal osteosarcoma, a prognostically favorable osteosarcoma subtype, was characterized by the presence of a ring chromosome accompanied by no or few other abnormalities. Complex karyotypes were seen nearly exclusively in the high-grade lesions. These findings indicate that specific chromosomal bands and/or regions are nonrandomly involved in osteosarcoma and may provide useful clinical information.

Adolescent↗
PubMed1997

Regulation of MMP-9 (92 kDa type IV collagenase/gelatinase B) expression in stromal cells of human giant cell tumor of bone.

Matrix metalloproteinases (MMPs) play an important regulatory role in tissue morphogenesis, cell differentiation, tumor invasion and metastasis. Several authors have reported a direct correlation between the production of 72 kDa (MMP-2) and 92 kDa (MMP-9) type IV collagenases/gelatinases and the metastatic potential of cancer cells. Recently, we have identified the expression of both MMP-2 and MMP-9 in primary cultures of human giant cell tumor (GCT) of bone in vitro, and in tissue extracts in vivo. Interestingly, MMP-9 is not secreted by late-passaged GCT cells. It is possible that the production of MMP-9 is regulated by certain factor(s) secreted by the multinucleated giant cells in the primary culture. In order to test this hypothesis, the effect of primary-culture-conditioned medium on the expression of MMP-9 by late-passaged mononuclear stromal cells was examined. Adding conditioned medium from the primary GCT culture to the late-passaged stromal cells induced MMP-9, as evidenced by the presence of lytic bands at M(r) 92,000 and 72,000 on a gelatin zymogram. These enzyme activities were inhibited by EDTA, a well-known inhibitor of the MMPs. We confirmed these results by Western blotting using specific antibodies and RT-PCR for MMP-2 and MMP-9. Immunofluorescence studies with specific antibodies to MMP-9 further confirmed its expression by the passaged stromal cells cultured in the primary-culture-conditioned medium. The data indicate that MMP-2 and MMP-9 are produced by the mononuclear stromal cells when cultured in GCT primary-culture-conditioned medium. This suggests that multinucleated giant cells in primary cultures secrete a factor(s) that stimulates stromal cells to produce MMP-9, which, in turn, may contribute to the aggressive behavior of GCT.

Adolescent↗
PubMed1997

Familial aggregation of psychiatric disorders in a community sample of adolescents.

OBJECTIVE: To determine whether specific psychiatric disorders and suicide attempts ascertained in a community sample of adolescents show evidence of familial aggregation. METHOD: Fifty-eight adolescent probands recruited from the community and their relatives were assessed as to the presence of specific DSM-III Axis I disorders and suicide attempt, using a combination of family study and family history methodology. RESULTS: In first-degree relatives, there was evidence for specific familial aggregation of suicide attempt (odds ratio [OR] = 12.1 95% confidence interval [CI] = 1.3 to 111.0), substance abuse (OR = 2.7, 95% CI = 1.1 to 6.7), and any Axis I disorder (OR = 2.5, 95% CI = 1.3 to 4.6), even after demographic confounders and familial comorbidity were controlled. Similarly, among second-degree relatives, in analyses controlling for potentials confounders, the disorders-specific aggregation of suicide attempt (OR = 12.3, 95% CI = 1.2 to 130.0), substance abuse (OR = 2.8, 95% CI = 1.6 to 4.8), and any Axis I disorder (OR = 1.5, 95% CI = 1.0 to 2.2) persisted. CONCLUSIONS: The familial aggregation of suicide attempts and psychiatric disorders, particularly of substance abuse and any Axis I disorder, occurs in community samples and is not primarily attributable to referral status.

Adolescent↗
PubMed1997

Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma.

The pathogenesis of myxoid chondrosarcoma (CS) is poorly understood. A recurrent translocation, t(9;22) (q22;q12), has been recognized in CS, specifically in extraskeletal myxoid CS. Recently, this translocation has been shown to represent a rearrangement of the EWS gene at 22q12 with a novel gene at 9q22 designated CHN (or TEC). Sequence analysis suggests that CHN encodes a novel orphan nuclear receptor with a zinc finger DNA-binding domain. The structure of this gene fusion has been characterized in only a limited number of extraskeletal myxoid CSs and its presence in other types of CS has not been extensively examined. We studied 46 cases of CS (8 extraskeletal myxoid, 4 skeletal myxoid, 4 mesenchymal, and 30 other) for the EWS/CHN gene fusion by reverse transcriptase polymerase chain reaction, Southern blotting, and long-range DNA polymerase chain reaction. The EWS/CHN gene fusion was present in 6 of 8 extraskeletal myxoid CSs and was not detected in any of the remaining cases, including the 4 skeletal myxoid CSs. The negative findings in the latter cases suggest that skeletal myxoid CS is pathogenetically distinct from its extraskeletal counterpart. Notably, 2 cases of extraskeletal myxoid CS showed neither an EWS/CHN fusion transcript nor EWS/CHN genomic fusion nor EWS or CHN genomic rearrangement, suggesting genetic heterogeneity within extraskeletal myxoid CS. Finally, we also provide evidence for alternative splicing of the 3' end of the fusion transcript. Extraskeletal myxoid CS thus represents yet another sarcoma type containing a gene fusion involving EWS.

Adult↗
PubMed1997

Der(16)t(1;16)(q21;q13) as a secondary structural aberration in yet a third sarcoma, extraskeletal myxoid chondrosarcoma.

Cytogenetic analysis of an extraskeletal myxoid chondrosarcoma revealed a der(16)t(1;16)(q21;q13) in addition to the t(9;22)(q22;12) described as characteristic for this chondrosarcoma clinicohistopathologic subtype. An identical der(16) has been identified as the most common secondary structural aberration in Ewing's sarcoma and alveolar rhabdomyosarcoma.

Chondrosarcoma↗
PubMed1996

Cytogenetic analysis of a malignant triton tumor and a malignant peripheral nerve sheath tumor and a review of the literature.

Cytogenetic analyses of malignant peripheral nerve sheath tumors (MPNST) and malignant triton tumors (MTT) are few to date. Two separate triton tumor specimens from one patient and a MPNST specimen from another patient, both with peripheral neurofibromatosis (NF-1, von Recklinghausen disease), showed complex near-triploid complements and partial deletion of the short arm of chromosome 1. Notably, a structural abnormality of chromosome 17 was detected in the MPNST, and loss of chromosome 22 was detected in the MTT. The genes for peripheral neurofibromatosis (NF-1) and central neurofibromatosis (NF-2) have been mapped to these two chromosomes respectively.

Adolescent↗
PubMed1996

Significance of extra copies of chromosome 20 and the long arm of chromosome 2 in hepatoblastoma.

Cytogenetic analysis of both primary and metastatic hepatoblastoma revealed the following abnormal chromosomal complements respectively: 46,XX,der(2)t(2;2)(p25;q21),der(22)t(1;22)(q22;p13) [6]/47,XX,der(2)t(2;2)(p25;q21),+20,der(22)t(1;22)q22;p13)[4]/47,XX,der (2)t(2;2)(p25;q21), +20[1], and 48,XX,der(2)t(2;2)(p25;q21),+12,+17, -18,+20,der(22)t(1;22)(q22;p13)[9]/50,XX,der(2)t(2;2)(p25;q21), +8,+12,+17,+20[4]. Two abnormalities, the chromosome 2 derivative and trisomy 20, are recurrent in hepatoblastoma, but the derivative involving chromosomes 1 and 22 is a novel abnormality.

Chromosome Aberrations↗
PubMed1996

Loss of an X chromosome in aggressive angiomyxoma of female soft parts: a case report.

Cytogenetic analysis of an aggressive angiomyxoma of the vulvar region of a 16-year-old female revealed loss of one X chromosome (45,X,-X) in eight of 20 metaphase cells analyzed. Fluorescence in situ hybridization (FISH) performed on disaggregated cells from paraffin embedded lesional tissue confirmed loss of an X chromosome in 31% of cells. Cytogenetic analysis performed on peripheral blood showed a normal chromosomal complement (46,XX). Thus, loss of one X chromosome appears to be confined to the neoplasm. This anomaly has not been previously described in aggressive angiomyxoma.

Adolescent↗
PubMed1996

Cytogenetic analysis of dedifferentiated chondrosarcoma.

Cytogenetic analysis of a dedifferentiated chondrosarcoma with a fibrosarcomatous component revealed the following chromosomal complement: 47,XX,i(1)(q10), add(6)(q13),+7,+8,t(10;12) (p11.2;q11.2),+14,-15,-17, add(19)(q13,4). Chromosome studies of dedifferentiated chondrosarcoma are sparse. Three of the anomalies in the present study are similar to those previously described in dedifferentiated chondrosarcoma.

Chondrosarcoma↗
PubMed1996

Translocation (X;18) in primary synovial sarcoma of the lung.

Primary sarcomas of the lung are extremely rare. Among the most common to occur in this location are leiomyosarcoma, fibrosarcoma, and hemangiopericytoma. Many difficulties are encountered when establishing these sarcoma diagnoses, or one of another pathologic type, because of overlapping histologic features and morphologic similarities between primary and metastatic lesions. In this study, the diagnosis of a primary monophasic synovial sarcoma of the lung was aided by the observation of the X;18 translocation characteristic of this neoplasm. To the best of our knowledge, this is the first cytogenetic report of a primary pulmonary synovial sarcoma.

Chromosomes, Human, Pair 18↗