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)

Rhabdoid tumours are rare aggressive tumours of infancy. The definition classically relies on a characteristic morphology and the inactivation of the hSNF5/INI1 tumour suppressor gene. This entity includes central nervous system tumours (ATRT), renal tumours (RTK) and soft-part tumours. Their rarity and morphological pleomorphism make the diagnosis often challenging. However, the recently introduced immunohistochemistry with anti-INI1 (anti-SMARCB1) antibody is a very useful diagnostic tool. Deletions at the 22q11.2 locus and mutations in hSNF5/INI1 sequence must be investigated in order to confirm the diagnosis and to give insights on a presumable germline mutation. Indeed, a predisposition may be found in up to 30% of cases. The treatment is based on aggressive chemotherapy, surgery and irradiation. The prognosis remains poor and the survival rate is below 30%, whatever the anatomic location. Understanding the role of hSNF5/INI1 within the SWI-SNF complex for the epigenetic regulation of transcription might drive the future targeted therapies.
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PMID:[Rhadboid tumours: hSNF/INI1 deficient cancers of early childhood with aggressive behaviour]. 2008 Apr 59

We report an 18 year old patient with mild intellectual disability who was diagnosed with a late onset teratoid/rhabdoid tumour by histological and immunohistochemical studies. Array-CGH studies, performed on a peripheral blood sample, showed a 3.4Mb deletion of chromosome 22q11.2, distal to the common DiGeorge syndrome (DGS) or Velocardiofacial syndrome (VCFs) region. This deletion is consistent with a diagnosis of distal 22q11.2 deletion syndrome. The deletion encompasses the INI1/SMARCB1 tumour suppressor gene. Biallelic inactivation of this gene is characteristic of atypical teratoid/rhabdoid tumours. Although several constitutional chromosome conditions are known to have increased susceptibility to various forms of cancer, very little is known regarding the magnitude of risk for malignancy associated with distal 22q11.2 deletion syndrome. In view of this finding we suggest that patients diagnosed with distal 22q11.2 deletion syndrome undergo careful prolonged monitoring for this type of tumour. This case demonstrates the need to carefully assess regions found to be deleted in individuals, referred for dysmorphia and/or developments delay, by array-CGH for the presence of genes known to be implicated in malignancy.
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PMID:Diagnosis of distal 22q11.2 deletion syndrome in a patient with a teratoid/rhabdoid tumour. 2118 75

Human SNF5 (hSNF5; INI1, SMARCB1 or BAF47) is a component of the human SWI/SNF chromatin remodelling complex and a tumour suppressor mutated in rhabdoid tumours. It also associates with the integrase of the human immunodeficiency virus (HIV)-1. We show by fluorescence loss in photobleaching that hSNF5 is constantly shuttling between the nucleus and the cytoplasm, raising the question of what the role of hSNF5 is in the cytoplasm. Here, we demonstrate that hSNF5 directly interacts with the GTPase dynamin-2 (DNM2) in the cytoplasm. DNM2 is a large GTPase involved in endocytosis and vesicle dynamics, which has been related to HIV-1 internalization. We show that hSNF5 colocalizes with DNM2 in endocytic vesicles. Depletion of hSNF5, but not of other components of the SWI/SNF complex, destabilizes DNM2 and impairs DNM2-dependent endocytosis. Furthermore, we show that hSNF5 inhibits assembly-stimulated DNM2 GTPase activity but not basal GTPase activity in vitro. Altogether, these results indicate that hSNF5 affects both the stability and the activity of DNM2, uncovering an unexpected role of hSNF5 in modulating endocytosis, and open new perspectives in understanding the role of hSNF5 in tumour genesis.
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PMID:Cytoplasmic interaction of the tumour suppressor protein hSNF5 with dynamin-2 controls endocytosis. 2385 97


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