Written | 2000-11 | Anne Marie Capodano |
Laboratoire de Cytogénétique Oncologique, Hpital de la Timone, 264 rue Saint Pierre, 13005 Marseille, France |
Identity |
ICD-Topo | C710-C714,C717-C719,C720-C725,C716 BRAIN, & CRANIAL NERVES, & SPINAL CORD, (EXCL. VENTRICLE, CEREBELLUM) / CEREBELLUM |
ICD-Morpho | 9400/3 Astrocytoma, NOS |
Atlas_Id | 5007 |
Phylum | Central Nervous system::Glioma |
WHO/OMS Classification | Central Nervous system |
Classification |
Note | Astrocytic tumors comprise a wide range of neoplasms that differ in their location within the central nervous system (CNS), age and gender distribution, growth potential, extent of invasiveness, morphological features, tendency for progression and clinical course; there is increasing evidence that these differences reflect the type and sequence of genetic alterations acquired during the process of transformation. |
The following clinicopathological entities can be distinguished : |
Clinics and Pathology |
Etiology | |
Epidemiology | diffuse astrocytomas are the most frequent intracranial neoplasm and account for more than 60% of all primary brain tumors; the incidence differs between regions, but there are 5 to 7 new cases per 100.000 population per year |
Clinics |
|
Pathology |
another subgroup of glioblastoma can be distinguished: the giant cell glioblastomas; histologically it is a glioblastoma with giant cells (500 mm in diameter): it develops clinically de novo ; it is associated with a favorable prognosis |
Treatment | treatment differs according to grade and location of tumor pilocytic astrocytomas can be cured by complete resection of tumor; if exeresis is not possible due to the location of the tumor, chemotherapy is indicated in young children and radiotherapy in adults in fibrillary astrocytomas, the treatment consists of total and extent resection of tumor in anaplastic tumors and glioblastoma multiforme, the treatment consists of total resection and radiotherapy and chemotherapy after surgery |
Prognosis | in low grade astrocytomas, a correlation of proliferation was reported (Ki67 index) with clinical outcome; the proliferative potential correlates inversely with survival and time to recurrence; the mean survival time after surgery is 6-8 years in low-grade astrocytomas; after surgery, the prognosis depends on whether the neoplasm undergoes progression to a more malignant phenotype; in pilocytic astrocytomas, total cure is possible after total resection; in fibrillary astrocytomas reccurrence is frequent . in anaplastic astrocytomas and in glioblastomas, evaluation of the extent of resection can be a prognostic factor; prognosis is generally poor (about one year); patients below 45 yrs have a considerably better prognosis than elderly patients; primary glioblastomas have a short clinical history with a poor prognosis; survival is better in secondary glioblastomas |
Cytogenetics |
Cytogenetics Morphological | loss or deletion of chromosome 13, 13q14-q31 is found in some glioblastomas trisomy 19 was reported in glioblastomas by cytogenetic and comparative genomic hybridization (CGH) analysis; the loss of 19q in 19q13.2-qter was detected by loss of heterozigocity (LOH) studies in glioblastomas deletion of chromosome 4q, complete or partial gains of chromosome 20 has been described; gain or amplification of 12q14-q21 has been reported the loss of chromosome Y might be considered, when it occurs in addition to other clonal abnormalities |
Genes involved and Proteins |
Note | it is known that the progression of the-cell cycle is controled by positive and negative regulators; some autors report alteration in cell-cycle gene expression in human brain tumors the p16 gene and the p15 gene are located in 9p21, a chromosome region commonly deleted in astrocytomas; expression of p16 gene is frequently altered in these tumors: in 33-68% of primary glioblastomas and 25% of anaplastic astrocytomas the Rb gene located on13q chromosome plays an important role in the malignant progression of gliomas the p53 gene is a tumor suppressor gene located on chromosome 17p13.1; loss or mutation of p53 gene has been detected in many types of gliomas and represents an early genetic event in these tumors overexpression of MDM2 is also seen in primary glioblastomas others oncogenes have been found to be amplified in a few cases of astrocytomas : oncogenes Gli, MYC, MYCN, MET and N-Ras in addition to p53 gene, others tumor suppression genes play a role in astrocytomas loss of chromosome 10 is the most frequent abnormality associated with the progression of malignant astrocytic tumors; more than 70% of glioblastomas show LOH on chromosome 10; amplification of EGFR is always associated with loss of chromosome 10 the PTEN gene located at the 10q23 locus is implicated more frequently in glioblastomas than in anaplastic astrocytomas another suppressor gene the MXII gene has also been located on the distal portion of chromosome 10 at the 10q24 at the 10q24-p25 locus homozygous deletion in the DMTB gene located on the region 10q25.3-26.1 have been reported in glioblastomas the LG11 novel gene located in 10p24 region is a suppressor gene rearranged in several glioblastomas tumors allelic loss of chromosome 22q wich contains the neurofibromatosis type 2, tumor suppressor gene NF2 is observed in 20-30% of astrocytomas. But another possibility is the involvement of another gene located on chromosome 22 in the tumorogenesis of astrocytomas most of these genes participate in the progression of astrocytomas (fig 1) the epidermal growth factor receptor (EGFR) coded by the EGFR cellular oncogene is located on human chromosome 7 at locus 7p12-p14; EGRF is amplified in 40-60% of glioblastomas; it constitues a hallmark: primary glioblastomas rarely contain EGFR overexpression; patients with anaplastic astrocytomas or glioblastomas have a poorer prognosis when EGFR gene amplification is present; amplification could be a significant prognostic factor in these tumors over expression of PDGFR-a (platelet derived growth factor) is asociated with loss of heterozygosity of chromosome 17p and p53 mutations in secondary glioblastomas others growth factors expressed in gliomas include fibroblast growth factors (FGFs), insulin-like growth factors (IGFs), and vascular endothelial growth factor (VEGF) |
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Molecular pathways in the progression of astrocytomas (from Ho-Keung and Paula Y.P. Lam) | |
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Citation |
This paper should be referenced as such : |
Capodano, AM |
Nervous system: Astrocytic tumors |
Atlas Genet Cytogenet Oncol Haematol. 2001;5(1):58-61. |
Free journal version : [ pdf ] [ DOI ] |
On line version : http://AtlasGeneticsOncology.org/Tumors/AstrocytID5007.html |
External links |
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