132 results on '"Brosjö O"'
Search Results
2. GM-CSF at Relatively high topic concentrations can significantly enhance the healing of surgically induced chronic wounds after radiotherapy
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Fernberg, J.-O., Brosjö, O., Friesland, S., and Masucci, G.
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- 2001
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3. Use of99mTc-MIBI scintigraphy in the evaluation of the response of osteosarcoma to chemotherapy
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Söderlund, V., Larsson, S. A., Bauer, H. C. F., Brosjö, O., Larsson, O., and Jacobsson, H.
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- 1997
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4. POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands#
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Möller, E, Stenman, G, Mandahl, N, Hamberg, H, Mölne, L, van den Oord, J J, Brosjö, O, Mertens, F, and Panagopoulos, I
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- 2008
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5. Identification of a novel amplicon at distal 17q containing the BIRC5/SURVIVIN gene in malignant peripheral nerve sheath tumours
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Storlazzi, C T, Brekke, H R, Mandahl, N, Brosjö, O, Smeland, S, Lothe, R A, and Mertens, F
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- 2006
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6. Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders
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Smeland, S, Müller, C, Alvegard, T.A, Wiklund, T, Wiebe, T, Björk, O, Stenwig, A.E, Willén, H, Holmström, T, Follerås, G, Brosjö, O, Kivioja, A, Jonsson, K, Monge, O, and Sæter, G
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- 2003
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7. Fine needle aspiration (FNA) cytology in the diagnosis of recurrent soft tissue sarcoma
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TROVIK, C. S., BAUER, H. C. F., BROSJÖ, O., SKOOG, L., and SÖDERLUND, V.
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- 1998
8. MR IMAGING OF SKELETAL MUSCLE HEMANGIOMAS: A report of 16 cases
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Jenner, G., Söderlund, V., Bauer, H. F.C., and Brosjö, O.
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- 1996
9. A comparison of Indomethacin and Diclofenac in the inhibition of experimental heterotopic new bone formation
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Nilsson, O. S., Bauer, H. C. F., Brosjö, O., and Törnkvist, H.
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- 1987
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10. Gain of 17q in malignant fibrous histiocytoma is associated with a longer disease-free survival and a low risk of developing distant metastasis.
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Weng, W-H., Åhlén, J., Lui, W-O., Brosjö, O., Pang, S-T., von Rosen, A., Auer, G., Larsson, O., Larsson, C., Ahlén, J, and Brosjö, O
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CANCER ,COMPARATIVE genomic hybridization ,GENETICS ,PATIENTS - Abstract
In this study, a panel of 39 primary malignant fibrous histiocytomas (MFH) of high malignancy grade were characterised for chromosomal alterations. The results were then evaluated in relation to the survival and the occurrence of recurrent disease during follow-up for an average period of 63 months. Chromosomal alterations detected by comparative genomic hybridisation (CGH) were recorded in 37 of the 39 cases analysed. The most frequent CGH abnormalities were gains of 17p, 20q, 16p, 17q, 1p31, 7q21, and 9cen-q22, and losses of 9p21-pter and 13q21-22. However, the patterns of CGH imbalances did not allow the identification of a single common event, suggesting that the key initiating event(s) is not a numerical imbalance. Patients with tumours harbouring a gain of 17q showed significantly longer overall and disease-free survival (P=0.001 and 0.008) as well as lower frequency of metastasis (P=0.018) during follow-up. Taken together, the findings suggest that the clinical outcome of MFH is associated with the genetic profiles of the primary tumours. Importantly, a subgroup of MFHs characterised by a low risk of developing metastasis and local recurrence is recognised based on their frequent gains of 17q by CGH. [ABSTRACT FROM AUTHOR]
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- 2003
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11. Intra-Articular Synovial Sarcomas: Incidence and Differentiating Features from Localized Pigmented Villonodular Synovitis.
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Nordemar, D., Öberg, J., Brosjö, O., and Skorpil, M.
- Abstract
Purpose. To determine the incidence of intra-articular synovial sarcomas and investigate if any radiological variables can differentiate them from localized (unifocal) pigmented villonodular synovitis (PVNS) and if multivariate data analysis could be used as a complementary clinical tool. Methods. Magnetic resonance images and radiographs of 7 cases of intra-articular synovial sarcomas and 14 cases of localized PVNS were blindedly reviewed. Variables analyzed were size, extra-articular growth, tumor border, blooming, calcification, contrast media enhancement, effusion, bowl of grapes sign, triple signal intensity sign, synovial low signal intensity, synovitis, age, and gender. Univariate and multivariate data analysis, the method of partial least squares-discriminant analysis (PLS-DA), were used. Register data on all synovial sarcomas were extracted for comparison. Results. The incidence of intra-articular synovial sarcomas was 3%. PLS-DA showed that age, effusion, size, and gender were the most important factors for discrimination between sarcomas and localized PVNS. No sarcomas were misclassified as PVNS with PLS-DA, while some PVNS were misclassified as sarcomas. Conclusions. The most important variables in differentiating intra-articular sarcomas from localized PVNS were age, effusion, size, and gender. Multivariate data analysis can be helpful as additive information to avoid a biopsy, if the tumor is classified as most likely being PVNS. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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12. Telomeric associations correlate with telomere length reduction and clonal chromosome aberrations in giant cell tumor of bone.
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Gebre-Medhin, S., Broberg, K., Jonson, T., Gorunova, L., Vult von Steyern, F., Brosjö, O., Y.Jin, Gisselsson, D., Panagopoulos, I., Mandahl, N., and Mertens, F.
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GIANT cell tumors ,CYTOGENETICS ,TELOMERES ,TELOMERIZATION ,IN situ hybridization ,CHROMOSOME abnormalities - Abstract
Giant cell tumor of bone (GCTB) is characterized cytogenetically by frequent telomeric associations (tas). To explore the mechanisms behind the formation of tas in GCTB and to investigate their karyotypic consequences, the frequencies of tas and clonal aberrations other than tas in 20 GCTBs were compared to telomere length and status, as assessed by quantitative PCR, fluorescence in situ hybridization (FISH), and expression levels of four genes involved in telomere maintenance. Based on the G-banding results, the tumors were divided into two groups, one with a high frequency of tas and one with a low frequency. Clonal aberrations were found to be restricted to the group with a high level of tas, and the same group showed a significantly larger reduction in telomere length in tumor cells compared to peripheral blood cells. Furthermore, 65 out of 66 tas analyzed by FISH were negative for telomeric sequences. The expression levels of TERT, TERF1, TERF2, and POT1 did not correlate with telomere length or the frequency of tas. Thus, the present findings provide strong support for the notion that decreased telomere length is a prerequisite for tas in GCTBs and that the clonal changes occurring in GCTBs are derived from tas. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
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- 2009
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13. Scandinavian experience in classical osteosarcoma: results of the SSG XIV protocol.
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Smeland S, Bruland ØS, Hjorth L, Brosjö O, Bjerkehagen B, Osterlundh G, Jakobson A, Hall KS, Monge OR, Björk O, and Alvegaard TA
- Abstract
Background and purpose The Scandinavian Sarcoma Group (SSG) XIV protocol was based upon the organisations experience from 3 previous osteosarcoma trials and was considered best standard of care for patients with extremity localised, non-metastatic osteosarcoma. We report the outcome of this protocol. Patients and methods From March 2001 to April 2005, 63 patients recruited from 10 centres in Finland, Sweden and Norway were included in this analysis. Patients received pre-operative chemotherapy consisting of 2 cycles of paired methotrexate (12 g/m2), cisplatin (90 mg/m2) and doxorubicin (75 mg/m2). Good histological responders continued with 3 cycles postoperatively whilst poor responders were salvaged with the addition of 3 cycles of ifosfamide (10DS12 g/m2). Outcome data was compared to previous SSG osteosarcoma trials. Results With a median follow-up of 64 months for survivors, the projected metastasis-free and sarcoma-related survivals at 5 years were 69% and 77%, respectively. 84% of the patients were treated with limb salvage surgery (49 patients) or rotationplasty (4 patients). 3 toxic deaths (5%) were recorded, all related to acute chemotherapy toxicity. The 5-year metastasis-free survival of patients receiving salvage therapy was 47% compared to 89% for good histological responders that only received the 3 drug combination postoperatively. Interpretation Outcome in the SSG XIV protocol compares favourably to previous SSG osteosarcoma trials and other published trials. The addition of ifosfamide to poor responders as an add on treatment did not improve outcome for poor responders to a similar level as for good responders. In a multi-institutional setting limb salvage surgery can safely be used in more than 80% of the patients. n [ABSTRACT FROM AUTHOR]
- Published
- 2009
14. Diagnostic procedures and surgical treatment of bone sarcomas.
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Brosjö, O. and Bauer, H. C. F.
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EWING'S sarcoma , *OSTEOSARCOMA , *SARCOMA , *BONE cancer , *TUMORS , *DISEASES - Abstract
Focuses on the progress in the diagnostic procedures and surgical treatment of patients with osteosarcoma and Ewing's sarcoma in Scandinavia. Use of amputation in treating the disease in the 1970s; Presentation of the local recurrence rate after local excision of osteosarcoma; Effectiveness of the adjuvant multidrug chemotherapy of patients with osteosarcoma applied as of 2004.
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- 2004
15. Chemotherapy in osteosarcoma.
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Smeland, S., Wiebe, T., Böhling, T., Brosjö, O., Jonsson, K., and Alvegård, T. A.
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DRUG therapy ,OSTEOSARCOMA ,SARCOMA ,BONE cancer ,DISEASES ,TUMORS ,TIBIA - Abstract
Examines the chemotherapy procedures applied to osteosarcoma patients by the Scandinavian Sarcoma Group. Common occurrence of the disease in children and adolescents particularly in the distal femur and proximal tibia; Low overall survival in methods used before the introduction of intensive polyagent chemotherapy; Rationale for preoperative chemotherapy which is to achieve immediate effect on metastatic disease.
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- 2004
16. Chemotherapy in Ewing's sarcoma.
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Smeland, S., Wiebe, T., Brosjö, O., Böhling, T., and Alvegård, T. A.
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EWING'S sarcoma ,OSTEOSARCOMA ,SARCOMA ,BONE cancer ,TREATMENT programs ,TUMORS ,CELLS - Abstract
Focuses on the experiences of the Scandinavian Sarcoma Group (SSG) in conducting two trials in Ewing's sarcoma, SSG IV and SSG IX. Composition of the Ewing's family of tumors (EFT) with Ewing's sarcoma, peripheral malignant neuroectodermal tumor and Askin's tumor; Malignancy of the tumors that are histologically composed of undifferentiated uniform small round cells with specific karotype; Administration of two treatment protocols for EFT, ISGSSG-3 and -4.
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- 2004
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17. Fine needle aspiration cytology in the diagnosis and management of children and adolescents with Ewing sarcoma and peripheral primitive neuroectodermal tumor*.
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Fröstad, B., Tani, E., Brosjö, O., Skoog, L., and Kogner, P.
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- 2002
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18. Use of [sup 99m] Tc-MIBI scintigraphy in the evaluation of the response of osteosarcoma to chemotherapy.
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Söderlund, V., Larsson, S. A., Bauer, H. C. F., Brosjö, O., Larsson, O., and Jacobsson, H.
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POSITRON emission tomography ,OSTEOSARCOMA ,TECHNETIUM - Abstract
The use of gamma camera scintigraphy with technetium-99m hexakis-2-methoxyisobutylisonitrile ([sup 99m]Tc-MIBI) for assessment of the response of highgrade osteosarcoma to preoperative chemotherapy was evaluated. Twelve patients with osteosarcoma of the extremities underwent planar examination with [sup 99m]TcMIBI before and after preoperative chemotherapy according to the recommendations of the Scandinavian Sarcoma Group. After calculating a quotient for the tumour and the average activity of both extremities and correcting for background activity, the change in uptake between the two examinations was assessed. This was compared with histological examination of the ultimately resected specimen in 11 patients and progressive clinical disease in one. All the 11 tumours undergoing histological examination showed cellular necrosis of between 50% and 100% as well as a reduced uptake of [sup 99m]TcMIBI, while the single progressive tumour showed an increased uptake. There was a correlation between the reduction of radiopharmaceutical uptake and the histological response in the entire series, while the variation was too large to allow conclusions in individual patients. This variation may have biological reasons or may be due to the planar imaging technique, which only allows semiquantitative evaluation. The technique reflects response to therapy but is not yet clinically applicable for the identification of poor responders, which would serve as a basis for alteration of the chemotherapy regimen. In order to evaluate whether such a role could be fulfilled, further studies using single-photon emission tomography with correction for attenuation and scattering of photons are necessary. [ABSTRACT FROM AUTHOR]
- Published
- 1997
19. Osteoid osteoma in a 1-year-old boy -- a case report.
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Ekström W, Söderlund V, and Brosjö O
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- 2006
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20. Disruption of the TP53 locus in osteosarcoma leads to TP53 promoter gene fusions and restoration of parts of the TP53 signalling pathway.
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Saba KH, Difilippo V, Kovac M, Cornmark L, Magnusson L, Nilsson J, van den Bos H, Spierings DC, Bidgoli M, Jonson T, Sumathi VP, Brosjö O, Staaf J, Foijer F, Styring E, Nathrath M, Baumhoer D, and Nord KH
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- Child, Adolescent, Humans, Genes, p53, Mutation, Promoter Regions, Genetic genetics, Gene Fusion, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Osteosarcoma genetics, Osteosarcoma pathology, Bone Neoplasms genetics, Bone Neoplasms pathology
- Abstract
TP53 is the most frequently mutated gene in human cancer. This gene shows not only loss-of-function mutations but also recurrent missense mutations with gain-of-function activity. We have studied the primary bone malignancy osteosarcoma, which harbours one of the most rearranged genomes of all cancers. This is odd since it primarily affects children and adolescents who have not lived the long life thought necessary to accumulate massive numbers of mutations. In osteosarcoma, TP53 is often disrupted by structural variants. Here, we show through combined whole-genome and transcriptome analyses of 148 osteosarcomas that TP53 structural variants commonly result in loss of coding parts of the gene while simultaneously preserving and relocating the promoter region. The transferred TP53 promoter region is fused to genes previously implicated in cancer development. Paradoxically, these erroneously upregulated genes are significantly associated with the TP53 signalling pathway itself. This suggests that while the classical tumour suppressor activities of TP53 are lost, certain parts of the TP53 signalling pathway that are necessary for cancer cell survival and proliferation are retained. In line with this, our data suggest that transposition of the TP53 promoter is an early event that allows for a new normal state of genome-wide rearrangements in osteosarcoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)
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- 2024
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21. Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma.
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Saba KH, Cornmark L, Hofvander J, Magnusson L, Nilsson J, van den Bos H, Spierings DC, Foijer F, Staaf J, Brosjö O, Sumathi VP, Lam SW, Szuhai K, Bovée JV, Kovac M, Baumhoer D, Styring E, and Nord KH
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- Adolescent, Adult, Bone Neoplasms pathology, Child, Child, Preschool, Enhancer Elements, Genetic, Epithelioid Cells pathology, Europe, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Osteoblastoma pathology, Osteogenesis, Phenotype, Wnt-5a Protein genetics, Young Adult, Biomarkers, Tumor genetics, Bone Neoplasms genetics, Gene Deletion, Gene Rearrangement, Neurofibromin 2 genetics, Osteoblastoma genetics, Proto-Oncogene Proteins c-fos genetics
- Abstract
Osteoblastoma is a locally aggressive tumour of bone. Until recently, its underlying genetic features were largely unknown. During the past two years, reports have demonstrated that acquired structural variations affect the transcription factor FOS in a high proportion of cases. These rearrangements modify the terminal exon of the gene and are believed to stabilise both the FOS transcript and the encoded protein, resulting in high expression levels. Here, we applied in-depth genetic analyses to a series of 29 osteoblastomas, including five classified as epithelioid osteoblastoma. We found recurrent homozygous deletions of the NF2 gene in three of the five epithelioid cases and in one conventional osteoblastoma. These events were mutually exclusive from FOS mutations. Structural variations were determined by deep whole genome sequencing and the number of FOS-rearranged cases was less than previously reported (10/23, 43%). One conventional osteoblastoma displayed a novel mechanism of FOS upregulation; bringing the entire FOS gene under the control of the WNT5A enhancer that is itself activated by FOS. Taken together, we show that NF2 loss characterises a subgroup of osteoblastomas, distinct from FOS-rearranged cases. Both NF2 and FOS are involved in regulating bone homeostasis, thereby providing a mechanistic link to the excessive bone growth of osteoblastoma., (© 2020 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.)
- Published
- 2020
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22. Genetic profiling of a chondroblastoma-like osteosarcoma/malignant phosphaturic mesenchymal tumor of bone reveals a homozygous deletion of CDKN2A, intragenic deletion of DMD, and a targetable FN1-FGFR1 gene fusion.
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Saba KH, Cornmark L, Rissler M, Fioretos T, Åström K, Haglund F, Rosenberg AE, Brosjö O, and Nord KH
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- Bone Neoplasms pathology, Chondroblastoma pathology, Cyclin-Dependent Kinase Inhibitor p16 genetics, Dystrophin genetics, Fibronectins genetics, Homozygote, Humans, Male, Mesenchymoma metabolism, Middle Aged, Osteosarcoma pathology, Receptor, Fibroblast Growth Factor, Type 1 genetics, Bone Neoplasms genetics, Chondroblastoma genetics, Gene Deletion, Mesenchymoma genetics, Oncogene Fusion, Osteosarcoma genetics
- Abstract
Conventional osteosarcoma is the most common primary malignancy of bone. This group of neoplasms is subclassified according to specific histological features, but hitherto there has been no correlation between subtype, treatment, and prognosis. By in-depth genetic analyses of a chondroblastoma-like osteosarcoma, we detect a genetic profile that is distinct from those previously reported in benign and malignant bone tumors. The overall genomic copy number profile was less complex than that typically associated with conventional osteosarcoma, and there was no activating point mutation in any of H3F3A, H3F3B, IDH1, IDH2, BRAF, or GNAS. Instead, we found a homozygous CDKN2A deletion, a DMD microdeletion and an FN1-FGFR1 gene fusion. The latter alteration has been described in phosphaturic mesenchymal tumor. This tumor type shares some morphological features with chondroblastoma-like osteosarcoma and we cannot rule out that the present case actually represents an FN1-FGFR1 positive malignant phosphaturic mesenchymal tumor of bone without osteomalacia., (© 2019 Wiley Periodicals, Inc.)
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- 2019
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23. Drug sensitivity testing on patient-derived sarcoma cells predicts patient response to treatment and identifies c-Sarc inhibitors as active drugs for translocation sarcomas.
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Brodin BA, Wennerberg K, Lidbrink E, Brosjö O, Potdar S, Wilson JN, Ma L, Moens LN, Hesla A, Porovic E, Bernhardsson E, Papakonstantinou A, Bauer H, Tsagkozis P, von Sivers K, Wejde J, Östling P, Kallioniemi O, and Stragliotto CL
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- Adult, CSK Tyrosine-Protein Kinase, Cell Line, Tumor, Drug Resistance, Neoplasm, Female, Humans, Male, Sarcoma genetics, Sarcoma pathology, Sarcoma drug therapy, src-Family Kinases antagonists & inhibitors
- Abstract
Background: Heterogeneity and low incidence comprise the biggest challenge in sarcoma diagnosis and treatment. Chemotherapy, although efficient for some sarcoma subtypes, generally results in poor clinical responses and is mostly recommended for advanced disease. Specific genomic aberrations have been identified in some sarcoma subtypes but few of them can be targeted with approved drugs., Methods: We cultured and characterised patient-derived sarcoma cells and evaluated their sensitivity to 525 anti-cancer agents including both approved and non-approved drugs. In total, 14 sarcomas and 5 healthy mesenchymal primary cell cultures were studied. The sarcoma biopsies and derived cells were characterised by gene panel sequencing, cancer driver gene expression and by detecting specific fusion oncoproteins in situ in sarcomas with translocations., Results: Soft tissue sarcoma cultures were established from patient biopsies with a success rate of 58%. The genomic profile and drug sensitivity testing on these samples helped to identify targeted inhibitors active on sarcomas. The cSrc inhibitor Dasatinib was identified as an active drug in sarcomas carrying chromosomal translocations. The drug sensitivity of the patient sarcoma cells ex vivo correlated with the response to the former treatment of the patient., Conclusions: Our results show that patient-derived sarcoma cells cultured in vitro are relevant and practical models for genotypic and phenotypic screens aiming to identify efficient drugs to treat sarcoma patients with poor treatment options.
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- 2019
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24. Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated with local control and survival.
- Author
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Tsagozis P, Brosjö O, and Skorpil M
- Abstract
Background: Preoperative radiotherapy is often used to facilitate excision of soft-tissue sarcomas. We aimed define factors that affect local tumour control and patient survival., Methods: A single institution registry study of 89 patients with non-metastatic soft-tissue sarcomas having preoperative radiotherapy between 1994 and 2014. Radiologic (presence of peritumoural oedema and volume change following radiotherapy) and histopathologic (tumour volume, grade and surgical margin) parameters were recorded. Outcomes were the events of local recurrence, amputation, metastasis and death., Results: Local recurrence rate was low (12%) and marginal excision gave equal local control to wide excision. Pelvic localization was associated with a higher risk for amputation. The absence of peritumoural oedema on MRI defined a subgroup of tumours with more favourable oncologic outcome. Reduction of tumour volume following radiotherapy was also associated with better patient survival. Both these radiologic parameters were associated with lower tumour grade. Tumour necrosis was not significant for patient survival. The local complication rate, mainly wound healing problems and infection, was high (40%), but did not lead to any amputation., Conclusion: Preoperative radiotherapy of high-risk soft-tissue sarcomas allows for good local control rate at the expense of local wound complications, which are however manageable. Marginal excision is sufficient for local control. Absence of peritumoural oedema on MRI, as well as tumour size reduction following radiotherapy are associated to superior patient survival and can be used ass early prognostic factors.
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- 2018
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25. Different patterns of clonal evolution among different sarcoma subtypes followed for up to 25 years.
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Hofvander J, Viklund B, Isaksson A, Brosjö O, Vult von Steyern F, Rissler P, Mandahl N, and Mertens F
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- Chromosome Aberrations, Chromosome Banding, Chromosomes ultrastructure, Follow-Up Studies, Gene Fusion, Humans, Mutation, Nucleotides chemistry, Oncogene Proteins, Fusion genetics, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Transcription Factor CHOP genetics, Clonal Evolution, Liposarcoma genetics, Liposarcoma, Myxoid genetics, Neoplasm Recurrence, Local, Sarcoma genetics
- Abstract
To compare clonal evolution in tumors arising through different mechanisms, we selected three types of sarcoma-amplicon-driven well-differentiated liposarcoma (WDLS), gene fusion-driven myxoid liposarcoma (MLS), and sarcomas with complex genomes (CXS)-and assessed the dynamics of chromosome and nucleotide level mutations by cytogenetics, SNP array analysis and whole-exome sequencing. Here we show that the extensive single-cell variation in WDLS has minor impact on clonal key amplicons in chromosome 12. In addition, only a few of the single nucleotide variants in WDLS were present in more than one lesion, suggesting that such mutations are of little significance in tumor development. MLS displays few mutations other than the FUS-DDIT3 fusion, and the primary tumor is genetically sometimes much more complex than its relapses, whereas CXS in general shows a gradual increase of both nucleotide- and chromosome-level mutations, similar to what has been described in carcinomas.
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- 2018
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26. EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma.
- Author
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Ferrari S, Bielack SS, Smeland S, Longhi A, Egerer G, Sundby Hall K, Donati D, Kevric M, Brosjö O, Comandone A, Werner M, Monge O, Palmerini E, Berdel WE, Bjerkehagen B, Paioli A, Lorenzen S, Eriksson M, Gambarotti M, Tunn PU, Jebsen NL, Cesari M, von Kalle T, Ferraresi V, Schwarz R, Bertulli R, Kasparek AK, Grignani G, Krasniqi F, Sorg B, Hecker-Nolting S, Picci P, and Reichardt P
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bone Neoplasms pathology, Cisplatin administration & dosage, Cisplatin adverse effects, Doxorubicin administration & dosage, Doxorubicin adverse effects, Europe, Febrile Neutropenia chemically induced, Female, Humans, Ifosfamide administration & dosage, Ifosfamide adverse effects, International Cooperation, Male, Methotrexate administration & dosage, Methotrexate adverse effects, Middle Aged, Osteosarcoma pathology, Prospective Studies, Survival Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Neoplasms drug therapy, Osteosarcoma drug therapy
- Abstract
Introduction: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma., Methods: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study., Results: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity., Conclusions: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.
- Published
- 2018
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27. The effect of radiotherapy on fat content and fatty acids in myxoid liposarcomas quantified by MRI.
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Skorpil M, Rydén H, Wejde J, Lidbrink E, Brosjö O, and Berglund J
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- Biopsy, Cell Differentiation, Female, Humans, Lipoma pathology, Liposarcoma, Myxoid radiotherapy, Male, Middle Aged, Protons, Retrospective Studies, Soft Tissue Neoplasms radiotherapy, Tumor Burden, Fatty Acids chemistry, Liposarcoma diagnostic imaging, Liposarcoma, Myxoid diagnostic imaging, Magnetic Resonance Imaging, Soft Tissue Neoplasms diagnostic imaging
- Abstract
Background: Myxoid liposarcomas are highly radiosensitive. Consequently radiotherapy is often used pre-operatively to reduce tumor volume and lessen the post-operative deficit. In soft-tissue sarcomas therapy response is mainly evaluated using magnetic resonance imaging (MRI) and the fundamental criterion for a positive response is decreased tumor size. In myxoid liposarcomas an increased fat content is also known to occur as a response to radiotherapy., Objective: To highlight the difficulties of MRI for therapy response evaluation in irradiated myxoid liposarcomas, by using MRI Dixon techniques enabling objective quantification of proton density fat fraction (%) and the number of double bonds (ndb; unsaturation degree) of fatty acids. Secondly, to compare quantitative fat fraction measurements versus visual grading of fat content on T1-weighted images., Case Descriptions: Prior to surgery, two patients with myxoid liposarcoma were treated with 50Gy. Following radiotherapy, both tumors on MRI showed reduced size, elevated fat fraction and transformed fat fraction histograms with diverse changes of ndb, while histopathological specimens showed discordant treatment effects; one case having good response and the other having poor response., Conclusions: A decrease in tumor size and increase in fat content on MRI cannot be interpreted as positive therapy response in radiotherapy of myxoid liposarcomas. Our data also give further supporting evidence that differentiation and maturation of tumor cells is the cause for the lipoma-like areas seen after radiotherapy. Finally, quantitative MRI Dixon techniques are preferable to visual grading for estimating the fat content in lipomatous tumors., (Copyright © 2017 Elsevier Inc. All rights reserved.)
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- 2017
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28. Improved Prognosis for Patients with Ewing Sarcoma in the Sacrum Compared with the Innominate Bones: The Scandinavian Sarcoma Group Experience.
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Hesla AC, Tsagozis P, Jebsen N, Zaikova O, Bauer H, and Brosjö O
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- Bone Neoplasms mortality, Bone Neoplasms pathology, Bone Neoplasms radiotherapy, Bone Neoplasms surgery, Disease-Free Survival, Female, Humans, Male, Neoplasm Recurrence, Local, Prognosis, Prospective Studies, Sarcoma, Ewing pathology, Sarcoma, Ewing radiotherapy, Young Adult, Pelvic Bones, Sacrum, Sarcoma, Ewing mortality
- Abstract
Background: Treatment of Ewing sarcoma of the pelvic bones remains one of the most difficult tasks in the treatment of bone sarcomas. Whether surgery or radiation therapy is the best local treatment is still a matter of debate. The aim of the present study was to compare sacral and nonsacral sites with regard to the treatment and outcome of pelvic Ewing sarcomas., Methods: Patients with Ewing sarcoma of the osseous pelvis diagnosed between 1986 and 2011 were identified through the Scandinavian Sarcoma Group registry. Data regarding tumor size, local treatment (surgery or radiation therapy), metastatic disease, surgical margins, local recurrence, and overall survival were analyzed., Results: Of the 117 patients examined, eighty-eight had tumors in the innominate bones and twenty-nine, in the sacrum. Radiation therapy was the sole local treatment for 40% of the innominate bone tumors in contrast to 79% of the sacral tumors. The five-year disease-free survival rate in the latter group (66%) was greater than that in the group with tumors in the innominate bones (40%) (p = 0.02 adjusted for size)., Conclusions: Disease-free survival among patients with Ewing sarcoma was improved when the tumor was localized in the sacrum compared with the innominate bones, where these tumors are generally larger. Local radiation therapy alone appears to result in good local tumor control and may be the treatment of choice for sacral tumors., (Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.)
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- 2016
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29. Current Strategies for the Treatment of Aneurysmal Bone Cysts.
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Tsagozis P and Brosjö O
- Abstract
Aneurysmal bone cysts are benign bone tumors that usually present in childhood and early adulthood. They usually manifest as expansile osteolytic lesions with a varying potential to be locally aggressive. Since their first description in 1942, a variety of treatment methods has been proposed. Traditionally, these tumors were treated with open surgery. Either intralesional surgical procedures or en bloc excisions have been described. Furthermore, a variety of chemical or physical adjuvants has been utilized in order to reduce the risk for local recurrence after excision. Currently, there is a shift to more minimally invasive procedures in order to avoid the complications of open surgical excision. Good results have been reported during percutaneous surgery, or the use of embolization. Recently, sclerotherapy has emerged as a promising treatment, showing effective consolidation of the lesions and functional results that appear to be superior to the ones of open surgery. Lastly, non-invasive treatment, such as pharmaceutical intervention with denosumab or bisphosphonates has been reported to be effective in the management of the disease. Radiotherapy has also been shown to confer good local control, either alone or in conjunction to other treatment modalities, but is associated with serious adverse effects. Here, we review the current literature on the methods of treatment of aneurysmal bone cysts. The indication for each type of treatment along reported outcome of the intervention, as well as potential complications are systematically presented. Our review aims to increase awareness of the different treatment modalities and facilitate decision-making regarding each individual patient.
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- 2015
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30. Prognostic factors and follow-up strategy for superficial soft-tissue sarcomas: Analysis of 622 surgically treated patients from the scandinavian sarcoma group register.
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Tsagozis P, Bauer HC, Styring E, Trovik CS, Zaikova O, and Brosjö O
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Infant, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local epidemiology, Population Surveillance, Prognosis, Registries, Sarcoma pathology, Sarcoma surgery, Scandinavian and Nordic Countries epidemiology, Survival Analysis, Young Adult, Sarcoma epidemiology
- Abstract
Background and Objectives: Our study aimed to describe the clinical outcome of patients with superficial soft-tissue sarcomas (SSTS), define prognostic factors and provide evidence for a rational surveillance scheme., Methods: Data for 622 consecutive, surgically treated SSTS patients were retrieved from the Scandinavian Sarcoma Group Register. We assessed the rates of local recurrence (LR) and metastasis (M), as well as overall survival (OS), local recurrence free-survival (LRFS) and metastasis-free survival (MFS) of the cohort., Results: The incidence of LR and M was 9% and 12%, respectively. OS at 5 years was 79%, LRFS was 74% and MFS 76%. Factors that affected OS, LRFS, and MFS were tumor size and patient age. Additionally, tumor grade was an independent prognostic factor for LRFS. The majority of LR and M events were observed the first 2 years of follow-up. Clear surgical margins were correlated to lower risk for LR. Selected patients benefited from adjuvant radiotherapy., Conclusions: SSTS have a favourable prognosis, which is mainly determined by tumour-associated factors. Adequate surgical margins are important for local control, whereas radiotherapy has a secondary role. The data support current surveillance schemes, with a closer follow-up the first 2 years after surgery., (© 2015 Wiley Periodicals, Inc.)
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- 2015
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31. RNA sequencing of sarcomas with simple karyotypes: identification and enrichment of fusion transcripts.
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Hofvander J, Tayebwa J, Nilsson J, Magnusson L, Brosjö O, Larsson O, von Steyern FV, Domanski HA, Mandahl N, and Mertens F
- Subjects
- Adult, Female, Humans, RNA, Messenger genetics, Gene Fusion genetics, Oncogene Proteins, Fusion genetics, RNA, Messenger analysis, Sarcoma genetics, Sequence Analysis, RNA methods
- Abstract
Gene fusions are neoplasia-associated mutations arising from structural chromosomal rearrangements. They have a strong impact on tumor development and constitute important diagnostic markers. Malignant soft tissue tumors (sarcomas) constitute a heterogeneous group of neoplasms with >50 distinct subtypes, each of which is rare. In addition, there is considerable morphologic overlap between sarcomas and benign lesions. Several subtypes display distinct gene fusions, serving as excellent biomarkers. The development of methods for deep sequencing of the complete transcriptome (RNA-Seq) has substantially improved the possibilities for detecting gene fusions. With the aim of identifying new gene fusions of biological and clinical relevance, eight sarcomas with simple karyotypes, ie, only one or a few structural rearrangements, were subjected to massively parallel paired-end sequencing of mRNA. Three different algorithms were used to identify fusion transcripts from RNA-Seq data. Three novel (KIAA2026-NUDT11, CCBL1-ARL1, and AFF3-PHF1) and two previously known fusions (FUS-CREB3L2 and HAS2-PLAG1) were found and could be verified by other methods. These findings show that RNA-Seq is a powerful tool for detecting gene fusions in sarcomas but also suggest that it is advisable to use more than one algorithm to analyze the output data as only two of the confirmed fusions were reported by more than one of the gene fusion detection software programs. For all of the confirmed gene fusions, at least one of the genes mapped to a chromosome band implicated by the karyotype, suggesting that sarcomas with simple karyotypes constitute an excellent resource for identifying novel gene fusions.
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- 2015
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32. Giant hydatid cyst of the pelvis, femur and retroperitoneal space: surgical treatment with extended hemipelvectomy.
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Tsagozis P and Brosjö O
- Subjects
- Animals, Echinococcosis pathology, Femur pathology, Humans, Male, Middle Aged, Pelvis pathology, Retroperitoneal Space pathology, Treatment Outcome, Echinococcosis diagnosis, Echinococcosis surgery, Echinococcus pathogenicity, Hemipelvectomy methods, Pelvis surgery
- Abstract
Hydatid disease of the bone is a very rare manifestation of the disease, and is often associated with debilitating symptoms. We present a rare case of skeletal hydatidosis in a 56-year-old man who had been misdiagnosed for many years. Massive involvement of the pelvic bones and soft tissues was evident. An extended hemipelvectomy was performed in order to achieve resection of the affected segments with a clear surgical margin. The patient recovered uneventfully and there are no signs of recurrence of the disease., (2015 BMJ Publishing Group Ltd.)
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- 2015
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33. Reconstruction with modular megaprostheses for sarcomas of the lower extremity.
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Tsagkozis P, Brosjö O, and Bauer HC
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Amputation, Surgical, Bone Neoplasms mortality, Child, Female, Humans, Incidence, Male, Middle Aged, Prosthesis Design, Prosthesis Failure, Retrospective Studies, Sarcoma mortality, Survival Rate, Treatment Outcome, United Kingdom, Young Adult, Artificial Limbs classification, Bone Neoplasms surgery, Limb Salvage methods, Lower Extremity surgery, Orthopedic Procedures methods, Plastic Surgery Procedures methods, Sarcoma surgery
- Abstract
Limb-preserving surgery using modular megaprostheses for the reconstruction of large skeletal defects is currently the preferred treatment for sarcomas. The authors report the postoperative outcomes after skeletal resection for lower extremity sarcomas and the use of the METS cemented modular implant system (Stanmore Implants, Hertfordshire, United Kingdom) for reconstruction. They retrospectively studied 52 consecutive patients operated on from 2003 to 2012. There were 27 distal femur prostheses, 13 proximal femur, 11 proximal tibia, and 1 total femur implants. Patients were followed for a mean of 4.3 years. Overall patient survival, prosthesis survival, limb salvage rate, and secondary complications were documented. Five years postoperatively, prosthesis survival was 79%. Complications warranting implant revision surgery were documented in 15% of patients, whereas complications warranting surgery of any kind were observed in 27% of the patients. Nonmechanical complications, namely local relapse of the tumor and prosthetic infection, were the most common cause of prosthetic failure, accounting for 88% of major revision surgeries and 100% of amputations. Mechanical complications were rare, observed in only 6% of patients. No patients required secondary revision surgery. The limb salvage rate was 89%. Overall patient survival was 79% at 5 years and 71% at 10 years. The low risk for mechanical complications and the high limb salvage rate support the use of the METS modular megaprostheses for the reconstruction of skeletal defects following lower limb sarcoma surgery., (Copyright 2015, SLACK Incorporated.)
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- 2015
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34. Recurrent PRDM10 gene fusions in undifferentiated pleomorphic sarcoma.
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Hofvander J, Tayebwa J, Nilsson J, Magnusson L, Brosjö O, Larsson O, Vult von Steyern F, Mandahl N, Fletcher CD, and Mertens F
- Subjects
- Abnormal Karyotype, Humans, In Situ Hybridization, Fluorescence, Mediator Complex genetics, Real-Time Polymerase Chain Reaction, Repressor Proteins genetics, Reverse Transcriptase Polymerase Chain Reaction, Trans-Activators genetics, DNA-Binding Proteins genetics, Gene Fusion genetics, Sarcoma genetics, Soft Tissue Neoplasms genetics, Transcription Factors genetics
- Abstract
Purpose: Undifferentiated pleomorphic sarcoma (UPS) is defined as a sarcoma with cellular pleomorphism and no identifiable line of differentiation. It is typically a high-grade lesion with a metastatic rate of about one third. No tumor-specific rearrangement has been identified, and genetic markers that could be used for treatment stratification are lacking. We performed transcriptome sequencing (RNA-Seq) to search for novel gene fusions., Experimental Design: RNA-Seq, FISH, and/or various PCR methodologies were used to search for gene fusions and rearrangements of the PRDM10 gene in 84 soft tissue sarcomas., Results: Using RNA-Seq, two cases of UPS were found to display novel gene fusions, both involving the transcription factor PRDM10 as the 3' partner and either MED12 or CITED2 as the 5' partner gene. Further screening of 82 soft tissue sarcomas for rearrangements of the PRDM10 locus revealed one more UPS with a MED12/PRDM10 fusion. None of these genes has been implicated in neoplasia-associated gene fusions before., Conclusions: Our results suggest that PRDM10 fusions are present in around 5% of UPS. Although the fusion-positive cases in our series showed the same nuclear pleomorphism and lack of differentiation as other UPS, it is noteworthy that all three were morphologically low grade and that none of the patients developed metastases. Thus, PRDM10 fusion-positive sarcomas may constitute a clinically important subset of UPS., (©2014 American Association for Cancer Research.)
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- 2015
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35. Reconstruction of metastatic acetabular defects using a modified Harrington procedure.
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Tsagozis P, Wedin R, Brosjö O, and Bauer H
- Subjects
- Acetabuloplasty methods, Adult, Aged, Aged, 80 and over, Arthroplasty, Replacement, Hip methods, Bone Screws, Female, Humans, Male, Middle Aged, Plastic Surgery Procedures methods, Retrospective Studies, Survival Analysis, Treatment Outcome, Acetabulum surgery, Bone Neoplasms surgery
- Abstract
Background and Purpose: Metastases engaging the acetabulum result in significant disability. We investigated the outcome after curettage and reconstruction of the defect with a protrusio cage, retrograde screws, and a cemented total hip arthroplasty., Patients and Methods: We retrospectively identified 70 consecutive patients who were surgically treated for metastatic disease of the acetabulum between 1995 and 2012 using the above technique. The type of primary tumor, extent of the disease, degree of acetabular erosion, and type of implant used were identified. Patient and implant survival, complications, and functional outcome were recorded., Results: There were no mortalities in the perioperative period (30 days after surgery). Median overall patient survival was 12 months. Prosthesis survival was 92% at 1 year and 89% at 5 years. One third of the patients suffered a complication, the most frequent one being dislocation. The functional outcome was good. Multiple skeletal or visceral metastases and specific types of cancer were associated with poor patient survival., Interpretation: Reconstruction of metastatic acetabular defects using a protrusio cage stabilized with retrograde screws and a cemented total hip arthroplasty is a safe procedure that provides efficient relief of symptoms. Patients with extensive disease, especially when diagnosed with specific types of cancer, have a very poor prognosis. The complication rate is substantial, the most frequent being dislocation. However, revision surgery is seldom required and prosthesis survival is high.
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- 2015
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36. Femoral Metastasis from Penile Carcinoma: Report of 2 Cases.
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Braumann L, Tsagozis P, Wedin R, and Brosjö O
- Abstract
Purpose. Penile cancer rarely gives symptomatic skeletal metastases. Methods. We present 2 patients with squamous carcinoma of the penis who were surgically treated for metastases in the femur. Results. Both patients had pathological fractures and were operated on. In one case, the skeletal metastasis preceded any lymphatic spread of the disease, suggesting early haematogenous dissemination. Conclusions. Endoprosthetic reconstruction resulted in pain relief and restored the ambulatory capacity. Clinicians should be aware of the possibility for symptomatic bone metastases with a risk for pathological fracture in patients with penile cancer.
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- 2015
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37. Treatment of an aggressive aneurysmal bone cyst with percutaneous injection of polidocanol: a case report.
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Brosjö O and Tsagozis P
- Subjects
- Adolescent, Diagnosis, Differential, Female, Follow-Up Studies, Humans, Injections, Magnetic Resonance Imaging, Polidocanol, Polyethylene Glycols administration & dosage, Sclerosing Solutions therapeutic use, Shoulder Joint, Treatment Outcome, Bone Cysts, Aneurysmal diagnosis, Bone Cysts, Aneurysmal drug therapy, Joint Diseases diagnosis, Joint Diseases drug therapy, Polyethylene Glycols therapeutic use
- Abstract
Introduction: Aneurysmal bone cysts are benign tumours that usually present in childhood. Aggressive forms have been described, which are often treated with surgery that entails major resection and reconstruction. Polidocanol sclerotherapy has recently been reported to have excellent results and promises to replace operative treatments, but its efficacy in the case of aggressive aneurysmal bone cysts has not been documented., Case Presentation: An 18-year-old woman from Sweden presented with pain in her shoulder and a rapidly progressing cystic bone lesion. The differential diagnosis was a rare, aggressive form of aneurysmal bone cyst or a sarcoma of the proximal humerus. She was successfully treated using sequential percutaneous injections of polidocanol after exclusion of malignancy., Conclusions: Management of aggressive aneurysmal bone cysts has thus far relied on open surgery. We propose that non-operative treatment with polidocanol is efficient even in the aggressive form of the aneurysmal bone cyst.
- Published
- 2014
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38. Fusions involving protein kinase C and membrane-associated proteins in benign fibrous histiocytoma.
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Płaszczyca A, Nilsson J, Magnusson L, Brosjö O, Larsson O, Vult von Steyern F, Domanski HA, Lilljebjörn H, Fioretos T, Tayebwa J, Mandahl N, Nord KH, and Mertens F
- Subjects
- Adult, Carrier Proteins genetics, Carrier Proteins isolation & purification, Chromosome Banding, Endosomes genetics, Endosomes pathology, Female, Histiocytoma, Benign Fibrous pathology, Humans, In Situ Hybridization, Fluorescence, Intracellular Signaling Peptides and Proteins, Male, Membrane Glycoproteins genetics, Membrane Glycoproteins isolation & purification, Membrane Proteins isolation & purification, Middle Aged, Oncogene Proteins, Fusion isolation & purification, Polymorphism, Single Nucleotide, Protein Kinase C beta isolation & purification, Protein Kinase C-delta isolation & purification, Signal Transduction, Tetraspanin 30 genetics, Tetraspanin 30 isolation & purification, Histiocytoma, Benign Fibrous genetics, Membrane Proteins genetics, Oncogene Proteins, Fusion genetics, Protein Kinase C beta genetics, Protein Kinase C-delta genetics
- Abstract
Benign fibrous histiocytoma (BFH) is a mesenchymal tumor that most often occurs in the skin (so-called dermatofibroma), but may also appear in soft tissues (so-called deep BFH) and in the skeleton (so-called non-ossifying fibroma). The origin of BFH is unknown, and it has been questioned whether it is a true neoplasm. Chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, RNA sequencing, RT-PCR and quantitative real-time PCR were used to search for recurrent somatic mutations in a series of BFH. BFHs were found to harbor recurrent fusions of genes encoding membrane-associated proteins (podoplanin, CD63 and LAMTOR1) with genes encoding protein kinase C (PKC) isoforms PRKCB and PRKCD. PKCs are serine-threonine kinases that through their many phosphorylation targets are implicated in a variety of cellular processes, as well as tumor development. When inactive, the amino-terminal, regulatory domain of PKCs suppresses the activity of their catalytic domain. Upon activation, which requires several steps, they typically translocate to cell membranes, where they interact with different signaling pathways. The detected PDPN-PRKCB, CD63-PRKCD and LAMTOR1-PRKCD gene fusions are all predicted to result in chimeric proteins consisting of the membrane-binding part of PDPN, CD63 or LAMTOR1 and the entire catalytic domain of the PKC. This novel pathogenetic mechanism should result in constitutive kinase activity at an ectopic location. The results show that BFH indeed is a true neoplasm, and that distorted PKC activity is essential for tumorigenesis. The findings also provide means to differentiate BFH from other skin and soft tissue tumors. This article is part of a Directed Issue entitled: Rare cancers., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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39. Megaprosthetic reconstruction for periprosthetic or highly comminuted fractures of the hip and knee.
- Author
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Lundh F, Sayed-Noor AS, Brosjö O, and Bauer H
- Subjects
- Adult, Aged, Aged, 80 and over, Arthroplasty, Replacement, Hip adverse effects, Arthroplasty, Replacement, Knee adverse effects, Female, Follow-Up Studies, Fractures, Comminuted diagnostic imaging, Fractures, Comminuted surgery, Hip Fractures diagnostic imaging, Humans, Knee Injuries diagnostic imaging, Male, Middle Aged, Prosthesis Failure, Prosthesis Implantation methods, Radiography, Recovery of Function, Retrospective Studies, Treatment Outcome, Arthroplasty, Replacement, Hip methods, Arthroplasty, Replacement, Knee methods, Hip Fractures surgery, Hip Prosthesis, Knee Injuries surgery, Knee Prosthesis
- Abstract
Objectives: To present the experience of a tertiary referral hospital in the management of a case series with hip or knee fractures by using modular megaprosthesis., Patients and Methods: Seventeen consecutive patients with highly comminuted fractures of the knee (n = 2), periprosthetic fractures of knee (n = 10) or hip (n = 5) were included. Fractures were managed with modular megaprosthesis (including total hip in 2 cases). Postoperative complications like infection and instability and outcome measures like return to previous mobility and living were recorded., Results: The mean age at time of surgery was 77 years (25-91), and mean follow-up was 44 months (13-98). We had no intra-operative complications. There were 3 deep periprosthetic infections, 1 hip and 2 knee. In the hip group, including total femur patients, we had 2 dislocations (2/7), both managed with closed reduction. No aseptic loosening was seen. 15/17 patients regained walking ability, and 16 were discharged to independent living. Nine patients have died at the time of follow-up., Conclusions: In these often old and physically compromised patients with highly comminuted fractures or complicated periprosthetic fractures, modular megaprosthesis could be a good surgical option. It can provide immediate stability and allow early mobilization.
- Published
- 2014
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40. Integrative genome and transcriptome analyses reveal two distinct types of ring chromosome in soft tissue sarcomas.
- Author
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Nord KH, Macchia G, Tayebwa J, Nilsson J, Vult von Steyern F, Brosjö O, Mandahl N, and Mertens F
- Subjects
- Adult, Aged, Aged, 80 and over, Cyclin-Dependent Kinase 4 genetics, Female, Gene Amplification, Gene Expression Profiling, Genetic Association Studies, Genome, Human, HMGA2 Protein genetics, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-mdm2 genetics, Proto-Oncogene Proteins c-mdm2 metabolism, Retinoblastoma Protein genetics, Sarcoma metabolism, Sarcoma mortality, Soft Tissue Neoplasms metabolism, Soft Tissue Neoplasms mortality, Ring Chromosomes, Sarcoma genetics, Soft Tissue Neoplasms genetics, Transcriptome
- Abstract
Gene amplification is a common phenomenon in malignant neoplasms of all types. One mechanism behind increased gene copy number is the formation of ring chromosomes. Such structures are mitotically unstable and during tumor progression they accumulate material from many different parts of the genome. Hence, their content varies considerably between and within tumors. Partly due to this extensive variation, the genetic content of many ring-containing tumors remains poorly characterized. Ring chromosomes are particularly prevalent in specific subtypes of sarcoma. Here, we have combined fluorescence in situ hybridization (FISH), global genomic copy number and gene expression data on ring-containing soft tissue sarcomas and show that they harbor two fundamentally different types of ring chromosome: MDM2-positive and MDM2-negative rings. While the former are often found in an otherwise normal chromosome complement, the latter seem to arise in the context of general chromosomal instability. In line with this, sarcomas with MDM2-negative rings commonly show complete loss of either CDKN2A or RB1 -both known to be important for genome integrity. Sarcomas with MDM2-positive rings instead show co-amplification of a variety of potential driver oncogenes. More than 100 different genes were found to be involved, many of which are known to induce cell growth, promote proliferation or inhibit apoptosis. Several of the amplified and overexpressed genes constitute potential drug targets.
- Published
- 2014
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41. Recurrent chromosome 22 deletions in osteoblastoma affect inhibitors of the Wnt/beta-catenin signaling pathway.
- Author
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Nord KH, Nilsson J, Arbajian E, Vult von Steyern F, Brosjö O, Cleton-Jansen AM, Szuhai K, and Hogendoorn PC
- Subjects
- Adolescent, Adult, Child, Cluster Analysis, DNA Copy Number Variations, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Mutation, Polymorphism, Single Nucleotide, Young Adult, Bone Neoplasms genetics, Bone Neoplasms metabolism, Chromosome Deletion, Chromosomes, Human, Pair 22, Osteoblastoma genetics, Osteoblastoma metabolism, Wnt Signaling Pathway
- Abstract
Osteoblastoma is a bone forming tumor with histological features highly similar to osteoid osteoma; the discrimination between the tumor types is based on size and growth pattern. The vast majority of osteoblastomas are benign but there is a group of so-called aggressive osteoblastomas that can be diagnostically challenging at the histopathological level. The genetic aberrations required for osteoblastoma development are not known and no genetic difference between conventional and aggressive osteoblastoma has been reported. In order to identify recurrent genomic aberrations of importance for tumor development we applied cytogenetic and/or SNP array analyses on nine conventional and two aggressive osteoblastomas. The conventional osteoblastomas showed few or no acquired genetic aberrations while the aggressive tumors displayed heavily rearranged genomes. In one of the aggressive osteoblastomas, three neighboring regions in chromosome band 22q12 were homozygously deleted. Hemizygous deletions of these regions were found in two additional cases, one aggressive and one conventional. In total, 10 genes were recurrently and homozygously lost in osteoblastoma. Four of them are functionally involved in regulating osteogenesis and/or tumorigenesis. MN1 and NF2 have previously been implicated in the development of leukemia and solid tumors, and ZNRF3 and KREMEN1 are inhibitors of the Wnt/beta-catenin signaling pathway. In line with deletions of the latter two genes, high beta-catenin protein expression has previously been reported in osteoblastoma and aberrations affecting the Wnt/beta-catenin pathway have been found in other bone lesions, including osteoma and osteosarcoma.
- Published
- 2013
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42. Comprehensive genetic analysis identifies a pathognomonic NAB2/STAT6 fusion gene, nonrandom secondary genomic imbalances, and a characteristic gene expression profile in solitary fibrous tumor.
- Author
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Mohajeri A, Tayebwa J, Collin A, Nilsson J, Magnusson L, von Steyern FV, Brosjö O, Domanski HA, Larsson O, Sciot R, Debiec-Rychter M, Hornick JL, Mandahl N, Nord KH, and Mertens F
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Female, High-Throughput Nucleotide Sequencing, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Male, Middle Aged, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Transcriptome, Young Adult, Oncogene Proteins, Fusion genetics, Repressor Proteins genetics, STAT6 Transcription Factor genetics, Solitary Fibrous Tumors genetics
- Abstract
Solitary fibrous tumor (SFT) is a mesenchymal neoplasm displaying variable morphologic and clinical features. To identify pathogenetically important genetic rearrangements, 44 SFTs were analyzed using a variety of techniques. Chromosome banding and fluorescence in situ hybridization (FISH) showed recurrent breakpoints in 12q13, clustering near the NAB2 and STAT6 genes, and single nucleotide polymorphism array analysis disclosed frequent deletions affecting STAT6. Quantitative real-time PCR revealed high expression levels of the 5'-end of NAB2 and the 3'-end of STAT6, which at deep sequencing of enriched DNA corresponded to NAB2/STAT6 fusions. Subsequent reverse-transcriptase PCR (RT-PCR) analysis identified a NAB2/STAT6 fusion in 37/41 cases, confirming that this fusion gene underlies the pathogenesis of SFT. The hypothesis that the NAB2/STAT6 fusions will result in altered properties of the transcriptional co-repressor NAB2--a key regulator of the early growth response 1 (EGR1) transcription factor - was corroborated by global gene expression analysis; SFTs showed deregulated expression of EGR1 target genes, as well as of other, developmentally important genes. We also identified several nonrandom secondary changes, notably loss of material from 13q and 14q. As neither chromosome banding nor FISH analysis identify more than a minor fraction of the fusion-positive cases, and because multiple primer combinations are required to identify all possible fusion transcripts by RT-PCR, alternative diagnostic markers might instead be found among deregulated genes identified at global gene expression analysis. Indeed, using immunohistochemistry on tissue microarrays, the top up-regulated gene, GRIA2, was found to be differentially expressed also at the protein level., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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43. Sclerotherapy with polidocanol for treatment of aneurysmal bone cysts.
- Author
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Brosjö O, Pechon P, Hesla A, Tsagozis P, and Bauer H
- Subjects
- Adolescent, Adult, Bone Cysts, Aneurysmal diagnostic imaging, Child, Child, Preschool, Female, Humans, Injections, Intralesional, Male, Musculoskeletal Pain etiology, Polidocanol, Radiography, Retrospective Studies, Treatment Outcome, Young Adult, Bone Cysts, Aneurysmal therapy, Polyethylene Glycols administration & dosage, Sclerosing Solutions administration & dosage
- Abstract
Background and Purpose: Recent data suggest that percutaneous sclerotherapy is a safe alternative to surgery for treatment of aneurysmal bone cysts (ABCs). We present our experience of this method., Methods: We retrospectively analyzed data from 38 consecutive patients treated with repeated injections of polidocanol. Each injection consisted of 2-4 mg polidocanol per kg body weight. Radiological and clinical assessments were performed until healing., Results: All cycts except 1 healed after a median of 4 (1-11) injections. A lesion failed to heal in 1 patient, who was operated. 3 patients experienced minor local inflammatory reactions., Interpretation: Our results show that percutaneus sclerotherapy with polidocanol has high efficacy in the treatment of ABCs, with a low frequency of side effects. Our findings corroborate data presented in previous publications. We believe that the method will be especially valuable in ABCs of the pelvis and sacrum, where surgery is associated with considerable morbidity.
- Published
- 2013
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44. A benign vascular tumor with a new fusion gene: EWSR1-NFATC1 in hemangioma of the bone.
- Author
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Arbajian E, Magnusson L, Brosjö O, Wejde J, Folpe AL, Nord KH, and Mertens F
- Subjects
- Adult, Bone Neoplasms pathology, Bone Neoplasms surgery, Chromosome Banding, Chromosomes, Human, Pair 22, Disease-Free Survival, Hemangioma pathology, Hemangioma surgery, Humans, In Situ Hybridization, Fluorescence, Male, Occipital Bone pathology, RNA-Binding Protein EWS, Reverse Transcriptase Polymerase Chain Reaction, Bone Neoplasms genetics, Calmodulin-Binding Proteins genetics, Hemangioma genetics, NFATC Transcription Factors genetics, Oncogene Proteins, Fusion, RNA-Binding Proteins genetics
- Abstract
The EWSR1 gene in chromosome band 22q12 is a promiscuous fusion partner involved in a vast array of tumors characterized by gene fusions. In this study, we report the finding of a new fusion gene, EWSR1-NFATC1, in a hemangioma of the bone; genetic rearrangements have not previously been described in this tumor type. Chromosome banding analysis showed a t(18;22)(q23;q12) translocation as the sole change. Fluorescence in situ hybridization mapping suggested the involvement of each of the 2 partner genes, and reverse transcriptase polymerase chain reaction revealed an in-frame EWSR1-NFATC1 transcript. NFATC1 has not previously been shown to be involved in a fusion chimera. However, NFATC2, encoding another member of the same protein family, is known to be a fusion partner for EWSR1 in a subgroup of Ewing sarcoma. Thus, our findings further broaden the spectrum of neoplasms associated with EWSR1 fusion genes, add a new partner to the growing list of EWSR1 chimeras, and suggest that chromosomal rearrangements of pathogenetic, and possibly also diagnostic, significance can be present in benign vascular bone tumors.
- Published
- 2013
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45. SNP array and FISH findings in two pleomorphic hyalinizing angiectatic tumors.
- Author
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Mohajeri A, Kindblom LG, Sumathi VP, Brosjö O, Magnusson L, Nilsson J, Nord KH, and Mertens F
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Blood Vessels pathology, Hyalin metabolism, In Situ Hybridization, Fluorescence, Polymorphism, Single Nucleotide genetics, Soft Tissue Neoplasms blood supply, Soft Tissue Neoplasms genetics
- Abstract
Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare soft tissue tumor of intermediate malignancy and uncertain cellular origin and lineage of differentiation. Although PHAT is still poorly characterized at the genetic level, there is a potential genetic overlap with two other soft tissue tumors: myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic fibrolipomatous tumor (HFLT); MIFS and HFLT share a characteristic t(1;10)(p22;q24) with breakpoints in the TGFBR3 locus on chromosome 1 and near the MGEA5 locus on chromosome 10. Recently, a PHAT with a similar t(1;10) was reported, suggesting a genetic link between MIFS/HFLT and PHAT. To ascertain whether PHAT is also associated with this translocation, two cases were subjected to single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization analyses. Neither PHAT showed a t(1;10) or other types of rearrangement of the TGFBR3 or MGEA5 loci. Both tumors showed imbalances in the SNP array analysis, but none was shared. Thus, the results indicate that PHAT is genetically distinguishable from MIFS and HFLT, but further studies are needed to identify the salient genetic pathways involved in PHAT development., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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46. The MDM2 SNP309 G allele is not preferentially amplified in bone and soft tissue tumors.
- Author
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Mertens F, Brosjö O, von Steyern FV, Nord KH, and Mandahl N
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Bone Neoplasms chemistry, Female, Gene Amplification, Humans, Liposarcoma chemistry, Liposarcoma genetics, Male, Middle Aged, Polymorphism, Single Nucleotide, Proto-Oncogene Mas, Proto-Oncogene Proteins c-mdm2 metabolism, RNA, Messenger genetics, Soft Tissue Neoplasms chemistry, Alleles, Bone Neoplasms genetics, Proto-Oncogene Proteins c-mdm2 genetics, Soft Tissue Neoplasms genetics
- Abstract
The transcriptional enhancer region in intron 1 of the proto-oncogene MDM2 contains a polymorphic site (SNP309) that may harbor a G or a T nucleotide. Previous studies have shown that the G allele confers a higher affinity for the Sp1 transcription factor, resulting in an increased transcriptional activity of MDM2. A constitutional G allele has also been associated with earlier onset of various cancer types, and studies of sarcomas have shown an enrichment of the G allele in tumors with MDM2 amplification, notably atypical lipomatous tumor (also known as well-differentiated liposarcoma). In the present study, we analyzed the SNP309 genotype in blood samples and tumor tissue from 57 patients with bone or soft tissue tumors showing amplification of MDM2. We did not observe any constitutional enrichment of the G allele. More importantly, there was no preferential amplification of the G allele in tumor tissue from TG heterozygotes. The expression levels of MDM2 messenger RNA were not higher in tumors with amplification of the G allele than in tumors with amplification of the T allele. Thus, we could not find any evidence for a selective advantage of the SNP309 G allele in bone and soft tissue tumors with MDM2 amplification., (Copyright © 2012. Published by Elsevier Inc.)
- Published
- 2012
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47. Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.
- Author
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Nord KH, Paulsson K, Veerla S, Wejde J, Brosjö O, Mandahl N, and Mertens F
- Subjects
- Adult, Chromosomes, Human, Pair 20, Chromosomes, Human, Pair 22, Chromosomes, Human, Pair 5, Cluster Analysis, Female, Gene Expression Profiling, Humans, Inflammation pathology, Leiomyosarcoma pathology, Loss of Heterozygosity, Male, Middle Aged, Neoplasm Staging, Polymorphism, Single Nucleotide, Young Adult, Gene Expression Regulation, Neoplastic, Leiomyosarcoma genetics, Uniparental Disomy
- Abstract
Inflammatory leiomyosarcoma (ILMS) is a soft tissue tumor that morphologically resembles conventional leiomyosarcoma (LMS) admixed with a prominent inflammatory infiltrate. Genetic data on ILMS are still limited but have suggested that this entity is characterized by hyperhaploidy (24-34 chromosomes). This low chromosome number is otherwise uncommon in neoplasia and has been found only in 0.2% to 0.3% of cytogenetically investigated tumors. Here, three ILMS were investigated using cytogenetic, single-nucleotide polymorphism (SNP) array, and global gene expression analyses. All cases displayed a hyperhaploid origin. Combined with previously reported cases, hyperhaploidy has been found in six of seven cytogenetically investigated ILMS. The copy number distribution of individual chromosomes is clearly nonrandom; the hyperhaploid clones of all six cases displayed disomy for chromosomes 5 and 20, and two copies of chromosomes 18, 21, and 22 were also common. All chromosomes identified as disomic showed a biparental origin by SNP array analysis; whether this is of pathogenetic importance is not known. Compared with conventional LMS, ILMS had a distinct gene expression signature. Furthermore, the number of chromosome copies correlated well with gene expression levels; disomic chromosomes showed higher gene expression levels than monosomic chromosomes, a finding that has not previously been reported for hyperhaploid tumors. Taken together, our findings suggest that disomy for some chromosomes, notably 5 and 20, as well as distorted gene expression achieved through massive loss of other chromosomes are essential features of ILMS.
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- 2012
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48. Recurrent rearrangement of the PHF1 gene in ossifying fibromyxoid tumors.
- Author
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Gebre-Medhin S, Nord KH, Möller E, Mandahl N, Magnusson L, Nilsson J, Jo VY, Vult von Steyern F, Brosjö O, Larsson O, Domanski HA, Sciot R, Debiec-Rychter M, Fletcher CD, and Mertens F
- Subjects
- Adult, Aged, Aged, 80 and over, Base Sequence, Bone Neoplasms pathology, Cell Shape, Chromosome Breakage, Chromosomes, Human genetics, Cytogenetic Analysis, Female, Fibroma, Ossifying pathology, Humans, In Situ Hybridization, Fluorescence, Male, Metaphase, Middle Aged, Molecular Sequence Data, Paraffin Embedding, Polycomb-Group Proteins, Polymerase Chain Reaction, Polymorphism, Single Nucleotide genetics, Recurrence, Bone Neoplasms genetics, DNA-Binding Proteins genetics, Fibroma, Ossifying genetics, Gene Rearrangement genetics, Transcription Factors genetics
- Abstract
Ossifying fibromyxoid tumor (OFMT) is a soft tissue tumor of unknown lineage. Although most cases are histologically and clinically benign, some show malignant morphological features and local recurrences are not uncommon; a few may even metastasize. In the present study, cytogenetic analysis identified different structural rearrangements of chromosome band 6p21 in tumor cells from three cases of OFMT, including one with typical, one with atypical, and one with malignant morphological features. Mapping of the 6p21 breakpoint by fluorescence in situ hybridization (FISH) indicated that the PHF1 gene was rearranged in all three cases. Further FISH, 5'-rapid amplification of cDNA ends, and RT-PCR analyses disclosed an EP400/PHF1 fusion transcript in one of the cases. Interphase FISH on tumor sections from 13 additional cases of OFMT showed rearrangement of the PHF1 locus in four of four typical, two of three atypical, and one of six malignant lesions. Thus, the PHF1 gene, previously shown to be the 3'-partner of fusion genes in endometrial stromal tumors, is also recurrently involved in the pathogenesis of OFMTs, irrespective of whether they are diagnosed as typical, atypical, or malignant lesions. The PHF1 protein interacts with the polycomb-repressive complex 2 (PRC2), which, in turn, regulates the expression of a variety of developmental genes. Thus, the results indicate that deregulation of PRC2 target genes is crucial for OFMT development., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2012
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49. Mesenchymal stromal cells from primary osteosarcoma are non-malignant and strikingly similar to their bone marrow counterparts.
- Author
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Brune JC, Tormin A, Johansson MC, Rissler P, Brosjö O, Löfvenberg R, von Steyern FV, Mertens F, Rydholm A, and Scheding S
- Subjects
- Adolescent, Cell Culture Techniques, Child, Female, Humans, Male, Middle Aged, Multipotent Stem Cells, Stromal Cells cytology, Tumor Microenvironment, Young Adult, Bone Marrow Cells cytology, Bone Neoplasms pathology, Mesenchymal Stem Cells cytology, Osteosarcoma pathology
- Abstract
Mesenchymal stromal cells (MSC) are multipotent cells that can be isolated from a number of human tissues. In cancer, MSC have been implicated with tumor growth, invasion, metastasis, drug resistance and were even suggested as possible tumor-initiating cells in osteosarcoma (OS). However, MSC from OS and their possible tumor origin have not yet been thoroughly investigated. Therefore, primary OS mesenchymal progenitors and OS-derived MSC were studied. OS samples contained very high frequencies of mesenchymal progenitor cells as measured by the colony-forming unit fibroblast (CFU-F) assay (median: 1,117 colonies per 10(5) cells, range: 133-3,000, n = 6). This is considerably higher compared to other human tissues such as normal bone marrow (BM) (1.3 ± 0.2 colonies per 10(5) cells, n = 8). OS-derived MSC (OS-MSC) showed normal MSC morphology and expressed the typical MSC surface marker profile (CD105/CD73/CD90/CD44/HLA-classI/CD166 positive, CD45/CD34/CD14/CD19/HLA-DR/CD31 negative). Furthermore, all OS-MSC samples could be differentiated into the osteogenic lineage, and all but one sample into adipocytes and chondrocytes. Genetic analysis of OS-MSC as well as OS-derived spheres showed no tumor-related chromosomal aberrations. OS-MSC expression of markers related to tumor-associated fibroblasts (fibroblast surface protein, alpha-smooth muscle actin, vimentin) was comparable to BM-MSC and OS-MSC growth was considerably affected by tyrosine kinase inhibitors. Taken together, our results demonstrate that normal, non-malignant mesenchymal stroma cells are isolated from OS when MSC culture techniques are applied. OS-MSC represent a major constituent of the tumor microenvironment, and they share many properties with BM-derived MSC., (Copyright © 2010 UICC.)
- Published
- 2011
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50. Results of the Scandinavian Sarcoma Group XIV protocol for classical osteosarcoma: 63 patients with a minimum follow-up of 4 years.
- Author
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Smeland S, Bruland OS, Hjorth L, Brosjö O, Bjerkehagen B, Osterlundh G, Jakobson A, Hall KS, Monge OR, Björk O, and Alvegaard TA
- Subjects
- Adolescent, Adult, Antibiotics, Antineoplastic administration & dosage, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bone Neoplasms drug therapy, Bone Neoplasms mortality, Chemotherapy, Adjuvant, Child, Cisplatin administration & dosage, Doxorubicin administration & dosage, Female, Finland, Follow-Up Studies, Humans, Ifosfamide administration & dosage, Male, Methotrexate administration & dosage, Norway, Osteosarcoma drug therapy, Osteosarcoma mortality, Sweden, Treatment Outcome, Young Adult, Bone Neoplasms surgery, Osteosarcoma surgery
- Abstract
Background and Purpose: The Scandinavian Sarcoma Group (SSG) XIV protocol is based on experience from previous SSG trials and other osteosarcoma intergroup trials, and has been considered the best standard of care for patients with extremity localized, non-metastatic osteosarcoma. We analyzed the outcome in 63 consecutive patients. Patients and methods From 2001 through 2005, 63 patients recruited from centers in Sweden, Norway, and Finland were included. They received preoperative chemotherapy consisting of 2 cycles of paired methotrexate (12 g/m²), cisplatin (90 mg/m²), and doxorubicin (75 mg/m²). 3 cycles were administered postoperatively, and poor histological responders were given 3 additional cycles of ifosfamide (10-12 g/m²) as a salvage strategy., Results: With a median follow-up of 77 months for survivors, the estimated metastasis-free and sarcoma-related survival at 5 years was 70% and 76%, respectively. 53 patients were treated with limb salvage surgery or rotationplasty and 2 patients experienced a local recurrence. 3 toxic deaths were recorded, all related to acute toxicity from chemotherapy. The 5-year metastasis-free survival of poor histological responders receiving add-on treatment with ifosfamide was 47%, as compared to 89% for good histological responders., Interpretation: Outcome from the SSG XIV protocol compares favorably with the results of previous SSG trials and other published osteosarcoma trials. However, salvage therapy given to poor responders did not improve outcome to a similar degree as for good responders. In a multi-institutional setting, more than four-fifths of the patients were operated with limb salvage surgery or rotationplasty, with few local recurrences.
- Published
- 2011
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