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)

Cellular, cytogenetic, and molecular evidence indicates that chromosome band 1p36 is often deleted in neuroblastoma cell lines and tumours, suggesting the presence of one or more tumour suppressor genes in this region. We used a multifaceted approach to analyse the commonly deleted region, 28 distal 1p-specific polymorphic loci were used to detect loss of heterozygosity (LOH) in a panel of primary neuroblastoma tumours. Thirty-two of 122 tumours (26%) demonstrated LOH at three or more loci. In addition, a patient with a constitutional deletion of 1p36.2-.3 and two neuroblastoma cell lines with 1p36 abnormalities were characterised by FISH. When combined with the LOH data, a single consensus region of deletion was defined proximally by PLOD and distally by D1S80, a region spanning approximately five megabases. Several proposed candidate tumour suppressor genes, including ID3, CDC2L1, DAN, PAX7, E2F2, TNFR2 and TCEB3, map outside of this region; however, the transcription factor HKR3 cannot be excluded. LOH for 1p is correlated with adverse clinical and biological features and a poor prognosis, but 1p LOH is not an independent predictor of overall survival. To identify additional candidate genes, an integrated physical map of 1p35-36 is being constructed. The current map includes 445 polymerase chain reaction (PCR)-formatted markers and 608 YACs. This map will help identify region-specific transcripts by direct selection and sequencing.
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PMID:Molecular analysis of the region of distal 1p commonly deleted in neuroblastoma. 951 32

We analysed DNA from 68 neuroblastoma tumours for loss of heterozygosity (LOH) on the distal chromosome 1p (1p-LOH) using PCR-based DNA polymorphisms. Fifteen tumours (22%) displayed 1p-LOH. The shortest region of overlap (SRO) for the deletions was defined proximally by marker D1S244 and distally by marker D1S80. The CDC2L1 locus, located on chromosome 1p36, has been put forward as a neuroblastoma tumour suppressor. We analysed coding regions of the CDC2L1 gene in a subset of aggressive neuroblastoma tumours with known allelic loss for different 1p-markers. Single-stranded conformation polymorphism, heteroduplex and sequencing analysis of tumour DNA did not reveal any significant changes in the coding region. Using a DNA sequence polymorphism, we showed, in a primary tumour with an interstitial allelic deletion, that this tumour had both alleles of the CDC2L1 locus retained in the tumour. Thus, we showed that the neuroblastoma tumour suppressor critical region on 1p in our material is defined by loci D1S244 and D1S80 and that the CDC2L1 locus is distal to the critical region.
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PMID:Delimitation of a critical tumour suppressor region at distal 1p in neuroblastoma tumours. 951 41