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J A Bridge

Publications and source records attributed to J A Bridge.

At least 19 recordsLinked to original sources
PubMed2004

Recurrent chromosomal imbalances and structurally abnormal breakpoints within complex karyotypes of malignant peripheral nerve sheath tumour and malignant triton tumour: a cytogenetic and molecular cytogenetic study.

BACKGROUND: Cytogenetic studies of malignant peripheral nerve sheath tumours (MPNSTs) and malignant triton tumours (MTTs) are rare. AIMS: To undertake cytogenetic analysis of these tumours. METHODS: Conventional cytogenetic analysis of 21 MPNSTs and MTTs from 17 patients (nine with peripheral neurofibromatosis (NF1)) was carried out using standard culture and harvesting procedures. For a more precise identification of composite structural rearrangements and marker chromosomes, spectral karyotypic analysis (SKY) was applied to a subset of cases. In addition, EGFR gene copy number was assessed by fluorescence in situ hybridisation (FISH) analysis in a subset of cases. RESULTS: Cytogenetic analysis revealed predominantly complex karyotypes. SKY analysis was useful in further defining many structural anomalies. Structural aberrations most frequently involved chromosomal bands or regions 1p31-36, 4q28-35, 7p22, 11q22-23, 19q13, 20q13, and 22q11-13. Overall, loss of chromosomal material was much more common than gain. Loss of chromosomes or chromosomal regions 1p36 (48%), 3p21-pter (52%), 9p23-pter (57%), 10 (48%), 11q23-qter (48%), 16/16q24 (62%), 17(43%), and 22/22q (48%), and gains of 7/7q (29%) and 8/8q (29%) were most prominent. These gains and losses were distributed equally between MPNST and MTT, demonstrating that these entities are similar with respect to recurrent genomic imbalances. Similarly, none of the recurrent chromosomal breakpoints or imbalances was restricted to either NF1 associated or sporadic MPNSTs. FISH analysis was negative for amplification. CONCLUSIONS: These cytogenetic and molecular cytogenetic findings expand the knowledge of chromosomal alterations in MPNST and MTT, and point to possible recurring regions of interest.

Adolescent↗
PubMed2002

Low frequency of somatic mutations in the FH/multiple cutaneous leiomyomatosis gene in sporadic leiomyosarcomas and uterine leiomyomas.

Germline mutations in the fumarate hydratase gene at 1q43 predispose to dominantly inherited skin and uterine leiomyomata and leiomyosarcomas. The enzyme, which is a component of the tricarboxylic acid cycle, acts as a tumour suppressor. To evaluate fumarate hydratase in respective sporadic tumours, we analysed a series of 26 leiomyosarcomas and 129 uterine leiomyomas (from 21 patients) for somatic mutations in fumarate hydratase and allelic imbalance around 1q43. None of the 26 leiomyosarcomas harboured somatic mutations in fumarate hydratase. Fifty per cent of leiomysarcomas tested showed evidence of allelic imbalance at 1q, but this was not confined to the vicinity of fumarate hydratase. Only 5% (seven out of 129) of the leiomyomas showed allele imbalance at 1q42-q43 and no somatic mutations in fumarate hydratase were observed. Our findings indicate that mutations in fumarate hydratase do not play a major role in the development of sporadic leiomyosarcomas or uterine leiomyomas

Adult↗
PubMed2001

Cytogenetic instability, predominantly involving chromosome 1, is characteristic of elastofibroma.

Elastofibroma, an unusual pseudotumor composed of excessive collagen and abnormal elastic fibers, has rarely been subjected to cytogenetic analysis. Only two cases have been previously defined, both of which demonstrated nonclonal abnormalities. In the present study, three cases of elastofibroma were cytogenetically analyzed. Abnormalities of the short arm of chromosome 1 were seen in all three cases (either clonally or as the most frequently involved region among nonclonal aberrations). In addition, a translocation involving chromosomes 8 and 12 was detected as a clonal rearrangement in one of the three cases. The observation of clonal abnormalities in elastofibroma suggests that this lesion may represent a neoplastic rather than a reactive process.

Aged↗
PubMed2001

Characterization of chromosome aberrations associated with soft-tissue leiomyosarcomas by twenty-four-color karyotyping and comparative genomic hybridization analysis.

Data on the chromosome aberrations associated with leiomyosarcomas of soft tissues are limited, complex, and incomplete. The aim of this study was to characterize genetic aberrations associated with this tumor group, to identify consistent regions of involvement and to determine correlations with clinical outcome. Chromosomes were prepared from 10 primary soft-tissue leiomyosarcoma samples, and preparations from four of them, plus the cell line SK-LMS-1, were suitable for analysis using 24-color karyotyping by multifluor fluorescence in situ hybridization. This method allowed rearranged chromosomes to be characterized, which would not have been possible by banding analysis alone. The remaining six chromosome preparations were analyzed using standard Giemsa banding. The chromosome imbalances associated with all the samples were determined by comparative genomic hybridization analysis. Taken together, the results show both intra- and intertumor heterogeneity and considerable complexity. Although no highly consistent rearrangements were found, some regions of the genome frequently were involved, including 1q21, 5p14-pter, and 20q13, which likely harbor genes that play a role in the pathogenesis of soft-tissue leiomyosarcomas. There were no obvious correlations between the chromosomal changes identified and available clinical details.

Adult↗
PubMed2001

Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents.

The unbalanced translocation, der(17)t(X;17)(p11.2;q25), is characteristic of alveolar soft part sarcoma (ASPS). We have recently shown that this translocation fuses the TFE3 transcription factor gene at Xp11.2 to ASPL, a novel gene at 17q25. We describe herein eight morphologically distinctive renal tumors occurring in young people that bear the identical ASPL-TFE3 fusion transcript as ASPS, with the distinction that the t(X;17) translocation is cytogenetically balanced in these renal tumors. A relationship between these renal tumors and ASPS was initially suggested by the cytogenetic finding of a balanced t(X;17)(p11.2;q25) in two of the cases, and the ASPL-TFE3 fusion transcripts were then confirmed by reverse transcriptase-polymerase chain reaction. The morphology of these eight ASPL-TFE3 fusion-positive renal tumors, although overlapping in some aspects that of classic ASPS, more closely resembles renal cell carcinoma (RCC), which was the a priori diagnosis in all cases. These tumors demonstrate nested and pseudopapillary patterns of growth, psammomatous calcifications, and epithelioid cells with abundant clear cytoplasm and well-defined cell borders. By immunohistochemistry, four tumors were negative for all epithelial markers tested, whereas four were focally positive for cytokeratin and two were reactive for epithelial membrane antigen (EMA) (one diffusely, one focally). Electron microscopy of six tumors demonstrated a combination of ASPS-like features (dense granules in four cases, rhomboid crystals in two cases) and epithelial features (cell junctions in six cases, microvilli and true glandular lumens in three cases). Overall, although seven of eight tumors demonstrated at least focal epithelial features by electron microscopy or immunohistochemistry, the degree and extent of epithelial differentiation was notably less than expected for typical RCC. We confirmed the balanced nature of the t(X;17) translocation by fluorescence in situ hybridization in all seven renal tumors thus analyzed, which contrasts sharply with the unbalanced nature of the translocation in ASPS. In summary, a subset of tumors previously considered to be RCC in young people are in fact genetically related to ASPS, although their distinctive morphological and genetic features justify their classification as a distinctive neoplastic entity. Finally, the finding of distinctive tumors being associated with balanced and unbalanced forms of the same translocation is to our knowledge, unprecedented.

Adolescent↗
PubMed2001

Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumor (IMT) is a rare, but distinctive mesenchymal neoplasm composed of fascicles of bland myofibroblasts admixed with a prominent inflammatory component. Genetic studies of IMTs have demonstrated chromosomal abnormalities of 2p23 and rearrangement of the anaplastic lymphoma kinase (ALK) gene locus. In a subset of IMTs, the ALK C-terminal kinase domain is fused with a tropomyosin N-terminal coiled-coil domain. In the current study, fusion of ALK with the clathrin heavy chain (CTLC) gene localized to 17q23 was detected in two cases of IMT. One of these cases exhibited a 2;17 translocation in addition to other karyotypic anomalies [46,XX,t(2;17)(p23;q23),add(16)(q24)].

Adult↗
PubMed2001

Extra copies of chromosomes 7, 8, 12, 19, and 21 are recurrent in adamantinoma.

Adamantinoma of long bones is a rare neoplasm predominantly involving the tibia. Cytogenetic studies of adamantinoma are few. Cytogenetic or molecular cytogenetic analysis of four adamantinomas, and a review of eleven cases in the literature reveals extra copies of chromosomes 7, 8, 12, 19, and 21 as recurrent in this neoplasm. Adamantinoma may be confused with a variety of primary and metastatic epithelial and mesenchymal neoplasms. Observation of these aneuploidies may be useful in establishing the diagnosis of adamantinoma.

Adolescent↗
PubMed2001

Primary malignant neuroepithelial tumors of the kidney: a clinicopathologic analysis of 146 adult and pediatric cases from the National Wilms' Tumor Study Group Pathology Center.

Primary malignant neuroepithelial tumors of the kidney (NETKs) comprise a group of primitive, highly malignant neoplasms that histologically and clinically are not well characterized. A large cohort of 146 of these tumors, occurring in adults and children, has been collected at a single depository site, the National Wilms' Tumor Study Group (NWTSG) Pathology Center. The authors undertook a systematic retrospective review of the histologic, ultrastructural, and clinical features of these tumors, based on materials collected by the NWTSG and the consultation files of one of the authors (J.B.B.). Histologic features were generally those of primitive neural tumors with varying amounts of rosettes and neuropil; however, a large proportion of cases displayed unusual features such as spindle cells, ganglion cells, clear cell sarcoma-like foci, rhabdoid cells, epithelioid cells, and organoid foci. CD99 staining had been performed on 69 cases and showed membranous staining in 65. The NETKs were present in patients with a wide age spectrum, ranging from 1 month to 72 years (median, 18 years). EWS/FLI1 fusion analysis using reverse transcriptase-polymerase chain reaction and immunohistochemical stains for cytokeratin, chromogranin, and epithelial membrane antigen were performed successfully on a subset of 45 cases with available paraffin blocks. Only 13 of the 45 were fusion-positive, and there was no correlation between fusion status and histology, presence of rosettes, ultrastructural features, or cytokeratin positivity. CD99-negative cases were usually fusion-negative (six of seven cases), and all three chromogranin-positive cases were fusion-negative. Tumor staging, performed on 72 clearly defined and quantifiable cases by using NWTSG criteria, indicated that these are aggressive tumors, because only six were Stage 1, compared with 16 Stage 2, 31 Stage 3, and 19 Stage 4 lesions. The authors conclude that NETKs are a somewhat diverse group of generally aggressive, high-grade lesions that may present in a wide age range and are difficult to characterize without immunohistochemistry and cytogenetics/molecular biology.

Adolescent↗
PubMed2001

Translocation t(1;3)(p36.3;q25) is a nonrandom aberration in epithelioid hemangioendothelioma.

The cytogenetic findings for two epithelioid hemangioendotheliomas are reported. An identical chromosomal translocation involving chromosomes 1 and 3 [t(1;3)(p36.3;q25)] was detected in both cases of epithelioid hemangioendothelioma, possibly representing a characteristic rearrangement for this histopathologic entity. The presence of clonal karyotypic abnormalities supports a neoplastic origin for the epithelioid variant of hemangioendothelioma. Identification of the 1;3 translocation may be useful diagnostically. Should additional studies confirm these data, this could lead to the identification of the gene(s) central to this neoplastic process.

Adult↗
PubMed2001

Primary monophasic synovial sarcoma of the pleura: five cases confirmed by the presence of SYT-SSX fusion transcript.

This study reports five cases of primary pleural monophasic synovial sarcomas and assesses the role of the SYT-SSX fusion transcript in the differential diagnosis. Patients had a mean age of 47 years with no gender predilection. Chest pain and pleural-based masses with effusions characterized the clinical presentations. Each patient underwent a complete surgical resection of the mass. The mean follow-up was 9 months, available in four patients. They were all alive, with no evidence of disease. Histologically, neoplasms were composed of densely packed fusiform cells focally alternating with less cellular areas. No epithelial differentiation was identified at the hematoxylin and eosin level. Keratin and epithelial membrane antigen reactivity was focal and present in four and two tumors, respectively. There was no immunoreactivity for CD34. RT-PCR studies for the presence of a SYT-SSX1 or SYT-SSX2 fusion transcript were positive in every tumor. In comparison, 10 localized fibrous tumors were immunohistochemically negative for keratin and epithelial membrane antigen and positive for CD34. A SYT-SSX fusion transcript was not identified in any of five localized fibrous tumors tested. Identification of the synovial sarcoma-specific chimeric transcript (SYT-SSX1 or SYT-SSX2), in conjunction with immunoperoxidase studies, can be extremely helpful in identifying cases of pleural monophasic synovial sarcoma.

Adolescent↗
PubMed2001

Two-year prediction of children's firesetting in clinically referred and nonreferred samples.

This study provides the first prospective evaluation of the course and predictors of children's involvement with fire over a 2-year period in 268 nonpatient and patient children (ages 6-13 yrs). Selected predictor variables obtained at initial (intake) assessment, which included fire-specific and general psychosocial measures, were examined in each sample using hierarchical logistic regression. Both samples reported heightened involvement in matchplay and firesetting at follow-up, though the frequency of each behavior was nearly four times higher in patients than in nonpatients. Fifty per cent and 59% of the initial firesetters in the nonpatient and patient samples, respectively, became recidivists. In the nonpatient sample, the child's initial involvement in firesetting and level of covert antisocial behavior were the only psychosocial predictors of follow-up firesetting that added incremental variance beyond demographics. In the patient sample, the child's initial involvement in fire-related acts and level of covert antisocial behavior were the only predictors of follow-up firesetting beyond any initial involvement in matchplay. The findings highlight somewhat different risk factors for subsequent firesetting in nonpatient and patient children, especially prior firesetting and matchplay, respectively, and bear implications for the prevention of firesetting recidivism.

Adolescent↗
PubMed2001

Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases.

PURPOSE: A specific TLS-CHOP fusion gene resulting from the t(12;16) is present in at least 95% of myxoid liposarcomas (MLS). Three common forms of the TLS-CHOP fusion have been described, differing by the presence or absence of TLS exons 6-8 in the fusion product. Type 5-2 (also known as type II) consists of TLS exons 1-5 fused to CHOP exon 2; type 7-2 (also known as type I) also includes TLS exons 6 and 7 in the fusion, whereas type 8-2 (also known as type III) fuses TLS exons 1-8 to CHOP exon 2. We sought to determine the impact of TLS-CHOP fusion transcript structure on clinical outcome in a group of well-characterized MLS cases. We also analyzed P53 status, because this parameter has been found to have a significant prognostic impact in other sarcomas with chromosomal translocations. METHODS: We analyzed TLS-CHOP fusion transcripts by reverse-transcription PCR using RNA extracted from frozen tissue in 82 MLS confirmed previously to harbor a CHOP rearrangement either by Southern blotting or by cytogenetic detection of the t(12;16). Parameters analyzed included age, location, size, percentage of round cell (RC) component, areas of increased cellularity, necrosis, and surgical margins. In 71 (87%) cases, adequate tumor tissue was available for immunohistochemical analysis of P53 status, using DO7 antibody. The Kaplan-Meier method, log-rank, and Cox regression tests were used for survival analyses. RESULTS: Most MLS were >10 cm (73%), arising in the thigh (70%), and localized at presentation (89%). RC component was <5% in 47 (57%) cases and > or =5% in 35 (43%). The TLS-CHOP fusion transcript was type 5-2 in 55 (67%), type 7-2 in 16 cases (20%), and type 8-2 in 8 (10%). One tumor had a unique variant fusion, between exon 6 TLS and exon 2 CHOP. Two other cases (2%) showed an EWS-CHOP fusion transcript. Overexpression of P53 (defined as > or =10% nuclear staining) was detected in 12 (17%) cases. High histological grade (defined as > or =5% RC; P < 0.01), presence of necrosis (> or =5% of tumor mass; P < 0.05), and overexpression of P53 (P < 0.001) correlated with reduced metastatic disease-free survival in localized tumors. The presence of negative surgical margins (P < 0.01) and extremity location (P = 0.02) were found to be significant in predicting local recurrence in the entire group as well as localized cases by univariate and multivariate analysis. Although there was no significant correlation between TLS-CHOP transcript type and histological grade or disease-specific survival, an association was found between the P53 status and type 5-2 fusion (P < 0.01). CONCLUSION: In contrast to some other translocation-associated sarcomas, the molecular variability of TLS-CHOP fusion transcript structure does not appear to have a significant impact on clinical outcome in MLS. Instead, high histological grade (> or =5% RC), presence of necrosis, and P53 overexpression are predictors of unfavorable outcome in localized MLS.

Adult↗
PubMed2000

Loss of 14q and 22q in gastrointestinal stromal tumors (pacemaker cell tumors).

Gastrointestinal stromal tumors (GISTs), also referred to as "gastrointestinal pacemaker cell tumors (GIPACT)" are mesenchymal neoplasms that are phenotypically similar to the interstitial cells of Cajal (ICC). Cytogenetic studies of this entity are rare and molecular cytogenetic studies utilizing chromosome-specific probes are nonexistent. In the current study, cytogenetic and molecular cytogenetic analysis of 12 histologically and immunohistochemically confirmed GISTs revealed loss of a whole chromosome 14 or region(s) of 14q in 8 tumors evaluated (67%) and loss of a whole chromosome 22 or region(s) of 22q in 8 (67%) patients. Loss of 14q and 22q were observed in histologically benign and malignant GISTs. Structural rearrangements of chromosome 1 were observed in 2 malignant GISTs. These findings indicate that loss of 14q and 22q are nonrandom, early events in GIST tumorigenesis and suggest that tumor suppressor genes responsible for the development of this neoplasm may be located on these chromosomal arms.

Adult↗
PubMed2000

Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: an intergroup rhabdomyosarcoma study.

A comparative genomic hybridization (CGH) approach provides identification of genomic gains and losses in a tumor specimen in a single experiment. Only 11 embryonal rhabdomyosarcomas (E-RMS) have previously been subjected to CGH. The underlying genetic events in this histologic subtype are not well defined. In this investigation, 12 E-RMS specimens from 10 patients entered into Intergroup Rhabdomyosarcoma Study (IRS) I-IV and two local patients were analyzed by CGH and fluorescence in situ hybridization (FISH). Gains of chromosomes or chromosomal regions 2 (50%), 7 (42%), 8 (67%), 11 (42%), 12 (58%), 13q21 (33%), and 20 (33%) and losses of 1p35-36.3 (42%), 6 (33%), 9q22 (33%), 14q21-32 (25%), and 17 (25%) were most prominent. Chromosomal regions 1p35-36.3 and 9q22 represent novel regions of loss. Importantly, loss of 9q22 corresponds to the locus of a putative tumor suppressor gene (PTCH), which has been shown to play a role in rhabdomyosarcoma in a mouse model of Gorlin syndrome. Loss of 1p36 corresponds to the locus for PAX7, a paired box containing gene characteristically altered in alveolar rhabdomyosarcoma. Moreover, loss of 1p36 is prominent in another common pediatric soft tissue tumor, neuroblastoma. Gains of 2, 7, 8, 12, and 13 and loss of 14 were seen in the sole prior E-RMS CGH series; thus, these data provide important confirmatory results. In contrast to this previous study, however loss, not gain, of chromosome 17 was observed in the current study. Chromosome 17 loss correlates well with previous descriptions of frequent allelic loss of 17p (TP53) in E-RMS. In summary, CGH and FISH analyses of 12 E-RMS specimens revealed novel genomic imbalances that may be useful in directing further molecular studies for the determination of E-RMS critically involved genes.

Adolescent↗
PubMed2000

Cytogenetic and molecular genetic techniques as adjunctive approaches in the diagnosis of bone and soft tissue tumors.

Important and meaningful advances have been made in mesenchymal tumor cytogenetics during the last two decades. A number of bone and soft tissue tumors have been shown to have recurrent, if not specific, chromosomal changes, particularly translocations. These changes not only serve as aids in the diagnosis and classification of bone and soft tissue tumors, especially in the differential diagnosis of those of confusing nature, but have also guided molecular studies in establishing the underlying genes involved. To date, a number of tumor-specific gene fusions have been identified and many have been shown to encode aberrant transcription factors. These key biological events in bone and soft tissue tumors are crucial not only to our understanding of the sarcomagenetic processes leading to the various tumors, but also ultimately in the design of specific therapies tailored to the genetic events in mesenchymal neoplasms.

Artificial Gene Fusion↗