Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytogenetic and molecular analysis of soft tissue tumours has yielded a wealth of new information over the past 10-15 years. Many soft tissue neoplasms show specific karyotypic aberrations which have proved to be diagnostically valuable, and have also assisted in the understanding of pathogenetic mechanisms and rationalisation of classification systems (e.g. lipomatous tumours and Ewing's sarcoma/PNET). In certain clinical subsets, especially round cell sarcomas and fatty neoplasms, determination of karyotype (whether by conventional analysis, FISH or RT-PCR) has proved often to be useful in the diagnostic setting. Additionally the recognition of clonal abnormalities in both benign neoplasms as well as lesions formerly thought to be non-neoplastic (e.g. inflammatory "pseudotumour") has prompted reassessment of biologic concepts with regard to growth control. Inherited molecular genetic defects which predispose to soft tissue neoplasia (e.g. NF-1, Li-Fraumeni syndrome) have been characterised, leading to a greater understanding of tumour suppressor genes. Mesenchymal differentiation genes, the modes of action of which may help to expunge concepts of histogenesis, are being characterised. It is becoming clear that there exist growth control genes (such as the HMGI family) which, irrespective of differentiation, play an important role in a wide range of different mesenchymal tumours. Additionally it is evident that different histologic types of sarcoma (e.g. variants of liposarcoma) show quite different abnormalities of cell cycle control (notably at the G1-S checkpoint) and it seems increasingly likely that certain genetic aberrations, identifiable either at the chromosomal or individual gene level, may prove to be of prognostic relevance in sarcomas and may also open novel therapeutic avenues. While the validity of all molecular genetic data depends totally on skilled histological diagnosis and grading, there has never been a better time for close collaboration between pathologists and basic scientists in the study of soft tissue neoplasia.
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PMID:Soft tissue tumours: the impact of cytogenetics and molecular genetics. 947 86

Deregulation of apoptosis has been implicated in the pathogenesis, spontaneous regression and treatment resistance of neuroblastoma. A newly recognised member of the tumour necrosis factor (TNF)-family of death receptors known as Apo-3 has been mapped to human chromosome 1p36.3, a region commonly deleted in aggressive neuroblastoma. Based on its localisation and function, Apo-3 is a candidate for the putative neuroblastoma tumour suppressor gene. Therefore we analysed mRNA expression of the Apo-3 receptor/ligand (Apo-3/Apo-3L) system in a representative panel of 18 neuroblastoma cell lines, 41 primary neuroblastoma and 13 ganglioneuromas/ganglioneuroblastomas by semi-quantitative RT-PCR. We compared the level of expression with the well-established prognostic factors age, stage, histology, MYCN-amplification and TrkA expression, as well as outcome. For comparison, we studied Apo-3/Apo-3L expression in 27 central nervous system (CNS) primitive neuroectodermal tumours/medulloblastomas (PNET/medulloblastoma) and in six normal brain samples. Neuroblastoma cell lines with 1p deletion and MYCN-amplification expressed significantly lower levels of Apo-3 (P=0.009 and P=0.03, respectively) compared with neuroblastoma cell lines without 1p deletion or MYCN-amplification. The mean expression level of Apo-3L was significantly higher in ganglioneuromas/ganglioneuroblastomas compared with neuroblastomas (P=0.001) and in normal brain compared with PNET/medulloblastoma (P<0.0001). Expression of Apo-3L was significantly associated with survival in neuroblastomas (P<0.049) and in PNET/medulloblastomas (P=0.01). Expression of Apo-3 was significantly associated with survival in PNET/medulloblastomas (P=0.03). Thus, the Apo-3 receptor/ligand system might be involved in the regulation of apoptosis in neuroblastomas and PNET.
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PMID:Expression of Apo-3 and Apo-3L in primitive neuroectodermal tumours of the central and peripheral nervous system. 1175 Aug 45

Supratentorial primitive neuroectodermal tumours (sPNETs) are malignant central nervous system tumours of childhood which are histologically characterized by poorly differentiated neuroepithelial cells with the capacity for divergent differentiation into glial, neuronal, myogenic or melanotic lines. The histological differential diagnosis between sPNET and glioblastoma multiforme (GBM) may be difficult, particularly as GBMs can sometimes demonstrate a poorly differentiated PNET-like phenotype. To identify molecular genetic markers that may distinguish sPNET and GBM, we investigated 12 cerebral sPNETs and six GBMs from paediatric patients for genetic alterations of the TP53, PTEN, CDKN2A, EGFR, CDK4 and MDM2 genes, as well as for allelic loss on chromosome arms 10q and 17p. Mutations of the TP53 tumour suppressor gene were found in one of 12 sPNETs (8%) and two of six GBMs (33%). None of the sPNETs but two of six GBMs (33%, including one GBM with a TP53 mutation) showed allelic losses on chromosome arm 17p. PTEN mutations were detected in one of 12 sPNET (8%) and one of six GBMs (17%). None of the sPNETs and GBMs carried a homozygous deletion involving the CDKN2A tumour suppressor gene. No amplification of the EGFR, CDK4 or MDM2 proto-oncogenes was detected. Taken together, our results indicate that paediatric GBMs differ from sPNETs by a higher incidence of allelic losses on 17p and TP53 mutations. In addition, the patterns of genetic alterations in sPNETs and paediatric GBMs appear to be distinct from those in cerebellar medulloblastomas and adult GBMs, respectively.
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PMID:Molecular genetic analysis of the TP53, PTEN, CDKN2A, EGFR, CDK4 and MDM2 tumour-associated genes in supratentorial primitive neuroectodermal tumours and glioblastomas of childhood. 1217 45