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Molecular classific...
Molecular classification of mucoepidermoid carcinomas-prognostic significance of the MECT1-MAML2 fusion oncogene.
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- Behboudi, Afrouz, 1967 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology,Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Enlund, Fredrik, 1968 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology,Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Winnes, Marta, 1979 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology,Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Andrén, Ywonne, 1956 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology,Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Nordkvist, Anders (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology,Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Leivo, Ilmo (författare)
- Departmentof Pathology, Haartman Institute and Helsinki University Central Hospital, Universityof Helsinki, Finland
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- Flaberg, Emilie (författare)
- Karolinska Institutet
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- Szekely, Laszlo (författare)
- Karolinska Institutet
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- Mäkitie, Antti (författare)
- Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland
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- Grenman, Reidar (författare)
- Department of Otorhinolaryngology — Head and Neck Surgery and Medical Biochemistry, University of Turku, Finland
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- Mark, Joachim (författare)
- Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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- Stenman, Göran, 1953 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology,Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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(creator_code:org_t)
- 2006
- 2006
- Engelska.
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 45:5, s. 470-81
- Relaterad länk:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Mucoepidermoid carcinomas (MECs) of the salivary and bronchial glands are characterized by a recurrent t(11;19)(q21;p13) translocation resulting in a MECT1-MAML2 fusion in which the CREB-binding domain of the CREB coactivator MECT1 (also known as CRTC1, TORC1 or WAMTP1) is fused to the transactivation domain of the Notch coactivator MAML2. To gain further insights into the molecular pathogenesis of MECs, we cytogenetically and molecularly characterized a series of 29 MECs. A t(11;19) and/or an MECT1-MAML2 fusion was detected in more than 55% of the tumors. Several cases with cryptic rearrangements that resulted in gene fusions were detected. In fusion-negative MECs, the most common aberration was a single or multiple trisomies. Western blot and immunohistochemical studies demonstrated that the MECT1-MAML2 fusion protein was expressed in all MEC-specific cell types. In addition, cotransfection experiments showed that the fusion protein colocalized with CREB in homogeneously distributed nuclear granules. Analyses of potential downstream targets of the fusion revealed differential expression of the cAMP/CREB (FLT1 and NR4A2) and Notch (HES1 and HES5) target genes in fusion-positive and fusion-negative MECs. Moreover, clinical follow-up studies revealed that fusion-positive patients had a significantly lower risk of local recurrence, metastases, or tumor-related death compared to fusion-negative patients (P = 0.0012). When considering tumor-related deaths only, the estimated median survival for fusion-positive patients was greater than 10 years compared to 1.6 years for fusion-negative patients. These findings suggest that molecularly classifying MECs on the basis of an MECT1-MAML2 fusion is histopathologically and clinically relevant and that the fusion is a useful marker in predicting the biological behavior of MECs.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Adult
- Aged
- Aged
- 80 and over
- Blotting
- Western
- Carcinoma
- Mucoepidermoid
- classification
- genetics
- Child
- DNA Primers
- Female
- Humans
- Immunohistochemistry
- In Situ Hybridization
- Fluorescence
- Karyotyping
- Male
- Microscopy
- Confocal
- Middle Aged
- Oncogene Proteins
- Fusion
- genetics
- Oncogenes
- Prognosis
- Reverse Transcriptase Polymerase Chain Reaction
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Behboudi, Afrouz ...
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Enlund, Fredrik, ...
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Winnes, Marta, 1 ...
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Andrén, Ywonne, ...
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Nordkvist, Ander ...
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Leivo, Ilmo
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visa fler...
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Flaberg, Emilie
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Szekely, Laszlo
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Mäkitie, Antti
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Grenman, Reidar
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Mark, Joachim
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Stenman, Göran, ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Genes, chromosom ...
- Av lärosätet
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Göteborgs universitet
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Högskolan i Skövde
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Karolinska Institutet