Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oligodendroglioma (ODG) constitute a specific type of gliomas, with a better prognosis than astrocytic tumours of similar grade. No clear criteria exist to differentiate astrocytoma from ODG, leading to a significant inter-observer variation in the diagnosis of ODG. ODG are genetically characterised by chromosomal lesions in the 1p36 and the 19q13.3 regions. ODG tumours without these lesions but with TP53 lesions or glioblastoma multiforme-like genetic lesions (loss of chromosome 10 and amplification of 7p) probably constitute a different entity with an oligodendroglial phenotype. Recent clinical trials have shown that ODG are sensitive to chemotherapy with 60-65% of patients responding, with a median response duration of 1-1.5 years. This holds for both low and high-grade ODG; the response rate in mixed oligoastrocytomas may be slightly less but is still better than that of pure astrocytic tumours. There is a strong correlation between a favourable response to chemotherapy and the presence of 1p36 and 19q13.3 lesions, suggesting this may be used to select patients for treatment. The presence of 1p lesions is also related to a longer progression free survival after radiation therapy, implicating that the assessment of the presence of 1p lesions is an important prognostic tool for ODG. The chemosensitivity of ODG is not limited to the PCV schedule. Ongoing trials are investigating whether adjuvant chemotherapy after surgery and radiation therapy provides better survival and quality of life in newly-diagnosed anaplastic ODG. However, even patients with a good response to chemotherapy will ultimately relapse. This calls for improvement of the chemotherapy schedules and for improvement of second line chemotherapy. In the near future molecular analysis may become an important tool to identify tumours that are likely to respond to chemotherapy.
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PMID:Chemotherapy of oligodendroglial tumours: current developments. 1087 73

Extracranial spread of neuroectodermal tumors is an unusual event, most frequently expected from glioblastomas and medulloblastomas. Single cases of metastatic oligodendrogliomas have been described, but no genetic data are reported. Oligodendrogliomas are characterized by distinct genetic alterations, i.e. loss of heterozygosity (LOH) of 1p and 19q; therefore, molecular genetic analysis of metastatic cases is of considerable interest. It may be instrumental in defining the distant tumor as metastatic oligodendroglioma and give clues to the genetic events associated with the highly malignant transformation. We present the case of a patient with multiple bone metastases from a cerebral oligodendroglioma. Oligodendroglioma grade II was the diagnosis both at original and second operation, performed 7 and 1 years before the extracranial dissemination. The extraneural spread presented before the local intracranial recurrence. The patient received procarbazine, lomustine, vincristine chemotherapy and radiotherapy after the second surgery. The computed tomography-guided biopsy of the bone lesions revealed tumor cells positive for GFAP, S-100 and Leu-7 and negative for cytokeratin, LCA and EMA. The genetic analysis of DNA from the original tumor, the bone metastasis and the autoptic brain tumor showed LOH of 1p; heterozygous deletion of CDKN2A/p 16 was detected as additional alteration in the metastasis and in the intracranial tumor at autopsy. TP53, MDM2 and CDKN2A/p14ARF genes were unchanged. Repeated brain surgery and extended survival may have acted as promoter of extraneural dissemination. Loss of CDKN2A most probably played an important role in the malignant progression: its involvement in metastatic potential remains to be clarified. Our data confirm that malignant transformation of oliogodendrogliomas may be undetected by histology and underscore the importance of genetic analysis. Coincidentally with intensive anticancer therapy, chemotherapy included, employed in patients with oligodendroglioma and the ensuing long survival, the frequency of metastatic oliogodendrogliomas may increase.
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PMID:Molecular genetic study of a metastatic oligodendroglioma. 1501 56

Recent studies have revealed a correlation between specific genetic changes, such as loss of chromosome 1p and 19q, and sensitivity of oligodendroglial neoplasm to radiotherapy and chemotherapy; epigenetic changes also play an important role in some tumors. In this retrospective study, we analyzed chromosomal alterations in 17 loci and promoter methylation status of 8 tumor-related genes in 49 oligodendroglial tumors (29 WHO grade II and 11 WHO grade III oligodendrogliomas; 7 WHO grade II and 2 WHO grade III oligoastrocytomas) using quantitative microsatellite analysis and methylation-specific polymerase chain reaction and correlated this information with clinical data. We also performed immunohistochemical stains for Ki-67 and O (6)-methyl guanine-DNA methyl transferase. Our results showed that the frequency of deletions in regions on 1p, 9p, 10q, 17p and 19q were 71.4%, 26.5%, 6.1%, 69.4% and 89.8%, respectively. Promoter methylation was detected in p14, p15, p16, p53, p73, PTEN, MGMT and RASSF1A genes in 24.5%, 6.1%, 46.9%, 0%, 6.1%, 42.9%, 53.1% and 77.6% of tumors, respectively. Statistical analysis identified that 9p22 loss, p73 methylation and p15 methylation were independently associated with reduced overall survival, and Ki-67 labeling index (LI) > or = 5%, 9p22 loss, no loss of 19q, p73 methylation, p14 methylation and unmethylated MGMT predicted shorter progression-free survival. Our findings suggest that the frequent deletion and hypermethylation of tumor-related genes may represent a mechanism of tumor development and progression and emphasize the importance of defining new molecular markers for predicting prognosis, tumor recurrence and therapeutic response in cancer management.
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PMID:Correlation among pathology, genetic and epigenetic profiles, and clinical outcome in oligodendroglial tumors. 1933 Aug 28

Oligodendroglioma is the quintessential molecularly-defined brain tumor. The characteristic whole-arm loss of the long arm of chromosome 1 and the short arm of chromosome 19 (1p/19q-codeletion) within the genome of these tumors facilitated the reproducible molecular identification of this subcategory of gliomas. More recently, recurrent molecular genetic alterations have been identified to occur concurrently with 1p/19q-codeletion, and definitively identify these tumors, including mutations in IDH1/2, CIC, FUBP1, and the TERT promoter, as well as the absence of ATRX and TP53 alterations. These findings provide a foundation for the consistent diagnosis of this tumor type, upon which a generation of clinical investigators have assembled a strong evidence base for the effective treatment of this disease with radiation and chemotherapy.
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PMID:Molecular background of oligodendroglioma: 1p/19q, IDH, TERT, CIC and FUBP1. 2654 48

It has become increasingly evident that morphologically similar gliomas may have distinct clinical phenotypes arising from diverse genetic signatures. To date, glial tumours from the Tunisian population have not been investigated. To address this, we correlated the clinico-pathology with molecular data of 110 gliomas by a combination of HM450K array, MLPA and TMA-IHC. PTEN loss and EGFR amplification were distributed in different glioma histological groups. However, 1p19q co-deletion and KIAA1549:BRAF fusion were, respectively, restricted to Oligodendroglioma and Pilocytic Astrocytoma. CDKN2A loss and EGFR overexpression were more common within high-grade gliomas. Furthermore, survival statistical correlations led us to identify Glioblastoma (GB) prognosis subtypes. In fact, significant lower overall survival (OS) was detected within GB that overexpressed EGFR and Cox2. In addition, IDH1R132H mutation seemed to provide a markedly survival advantage. Interestingly, the association of IDHR132H mutation and EGFR normal status, as well as the association of differentiation markers, defined GB subtypes with good prognosis. By contrast, poor survival GB subtypes were defined by the combination of PTEN loss with PDGFRa expression and/or EGFR amplification. Additionally, GB presenting p53-negative staining associated with CDKN2A loss or p21 positivity represented a subtype with short survival. Thus, distinct molecular subtypes with individualised prognosis were identified. Interestingly, we found a unique histone mutation in a poor survival young adult GB case. This tumour exceptionally associated the H3F3A G34R mutation and MYCN amplification as well as 1p36 loss and 10q loss. Furthermore, by exhibiting a remarkable methylation profile, it emphasised the oncogenic power of G34R mutation connecting gliomagenesis and chromatin regulation.
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PMID:Molecular Diagnostic and Prognostic Subtyping of Gliomas in Tunisian Population. 2695 5

Oligodendroglioma is defined by IDH mutation and 1p/19q codeletion. Normal TP53 status is also its molecular feature. We report a case of oligodendroglioma that acquired imbalanced 1p/19q codeletion and TP53 mutation at recurrence after temozolomide therapy. The primary and recurrent tumors shared IDH1 and TERT promoter mutations. Although 1p/19q was codeleted in the primary tumor, it was imbalanced in the recurrent tumor harboring TP53 mutation. The copy-neutral loss of heterozygosity might have imbalanced the 1p/19q codeletion, while temozolomide therapy possibly caused the TP53 mutation. Such phenomena, although rare, should be noted during the clinical treatment of oligodendrogliomas.
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PMID:Comparative molecular analysis of primary and recurrent oligodendroglioma that acquired imbalanced 1p/19q codeletion and TP53 mutation: a case report. 3278 87