دورية أكاديمية
Inferior survival for patients with malignant peripheral nerve sheath tumors defined by aberrant TP53.
| العنوان: | Inferior survival for patients with malignant peripheral nerve sheath tumors defined by aberrant TP53. |
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| المؤلفون: | Høland M; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Institute for Clinical Medicine, University of Oslo, Oslo, Norway., Kolberg M; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Danielsen SA; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Bjerkehagen B; Department of Oral Biology, University of Oslo, Oslo, Norway.; Department of Pathology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway., Eilertsen IA; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Hektoen M; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Mandahl N; Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden., van den Berg E; Department of Genetics, The University Medical Center Groningen, Groningen, The Netherlands., Smeland S; Institute for Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway., Mertens F; Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden., Sundby Hall K; Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway., Picci P; Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy., Sveen A; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Lothe RA; Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. rlothe@rr-research.no.; Institute for Clinical Medicine, University of Oslo, Oslo, Norway. rlothe@rr-research.no. |
| المصدر: | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2018 Nov; Vol. 31 (11), pp. 1694-1707. Date of Electronic Publication: 2018 Jun 26. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0285 (Electronic) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol |
| أسماء مطبوعة: | Publication: 2023- : [New York] : Elsevier Inc. Original Publication: Baltimore, MD : Williams & Wilkins, c1988- |
| مواضيع طبية MeSH: | Nerve Sheath Neoplasms/*genetics , Nerve Sheath Neoplasms/*pathology , Neurofibrosarcoma/*genetics , Neurofibrosarcoma/*pathology , Tumor Suppressor Protein p53/*genetics, Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Child ; Female ; Gene Amplification ; Genes, p53/genetics ; Humans ; Male ; Middle Aged ; Mutation ; Nerve Sheath Neoplasms/mortality ; Neurofibrosarcoma/mortality ; Prognosis ; Proto-Oncogene Proteins c-mdm2/genetics ; Young Adult |
| مستخلص: | Malignant peripheral nerve sheath tumor is a rare and aggressive disease with poor treatment response, mainly affecting adolescents and young adults. Few molecular biomarkers are used in the management of this cancer type, and although TP53 is one of few recurrently mutated genes in malignant peripheral nerve sheath tumor, the mutation prevalence and the corresponding clinical value of the TP53 network remains unsettled. We present a multi-level molecular study focused on aberrations in the TP53 network in relation to patient outcome in a series of malignant peripheral nerve sheath tumors from 100 patients and 38 neurofibromas, including TP53 sequencing, high-resolution copy number analyses of TP53 and MDM2, and gene expression profiling. Point mutations in TP53 were accompanied by loss of heterozygosity, resulting in complete loss of protein function in 8.2% of the malignant peripheral nerve sheath tumors. Another 5.5% had MDM2 amplification. TP53 mutation and MDM2 amplification were mutually exclusive and patients with either type of aberration in their tumor had a worse prognosis, compared to those without (hazard ratio for 5-year disease-specific survival 3.5, 95% confidence interval 1.78-6.98). Both aberrations had similar consequences on the gene expression level, as analyzed by a TP53-associated gene signature, a property also shared with the copy number aberrations and/or loss of heterozygosity at the TP53 locus, suggesting a common "TP53-mutated phenotype" in as many as 60% of the tumors. This was a poor prognostic phenotype (hazard ratio = 4.1, confidence interval:1.7-9.8), thus revealing a TP53-non-aberrant patient subgroup with a favorable outcome. The frequency of the "TP53-mutated phenotype" warrants explorative studies of stratified treatment strategies in malignant peripheral nerve sheath tumor. |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (TP53 protein, human) 0 (Tumor Suppressor Protein p53) EC 2.3.2.27 (MDM2 protein, human) EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) |
| تواريخ الأحداث: | Date Created: 20180628 Date Completed: 20190821 Latest Revision: 20230210 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1038/s41379-018-0074-y |
| PMID: | 29946184 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1530-0285 |
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| DOI: | 10.1038/s41379-018-0074-y |