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)

Natural killer (NK)/T-cell lymphoma is a special subtype of rare malignant lymphoma that is more prevalent in Asia than in America and Europe. This newly characterized haemato-lymphoid malignancy is highly aggressive and frequently present in nasal and upper aerodigestive sites. Several studies have reported the commonly deleted region of chromosome 6q21-25 in this particular type of lymphoma. To refine the smallest region of overlapping (SRO) deletion for localization of potential tumour suppressor (TS) genes, we performed loss of heterozygosity (LOH) and homozygosity mapping of deletion (HOMOD) analyses on 37 nasal and nasal-type NK/T-cell lymphoma patients using a panel of 25 microsatellite markers, covering the 6q21-q25 region. In all patients studied, LOH was detected in eight (89%) paired-sample patients, while hemizygous deletion was detected in three (11%) single-sample patients. Combination of the LOH and HOMOD results defined a distinct 3 Mb SRO on chromosome 6q25. Quantitative multiplex polymerase chain reaction analysis of 10 sequence-tagged sites further refined the putative TS-gene-containing region to a 2.6 Mb interval between TIAM2 and SNX9. Eighteen known genes/Unigene clusters and 25 hypothetical genes are located within this 2.6 Mb region, but none are previously identified TS genes. These results provide a framework for future positional cloning of novel TS gene(s) at 6q25.2-q25.3.
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PMID:A 2.6 Mb interval on chromosome 6q25.2-q25.3 is commonly deleted in human nasal natural killer/T-cell lymphoma. 1289 14

Prostate cancer, the most common male cancer in Western countries, is commonly detected with complex chromosomal rearrangements. Following the discovery of the recurrent TMPRSS2:ETS fusions in prostate cancer and EML4:ALK in non-small-cell lung cancer, it is now accepted that fusion genes not only are the hallmark of haematological malignancies and sarcomas, but also play an important role in epithelial cell carcinogenesis. However, previous studies aiming to identify fusion genes in prostate cancer were mainly focused on expression changes and fusion transcripts. To investigate the genes recurrently affected by the chromosome breakpoints in prostate cancer, we analysed Affymetrix array 6.0 and 500K SNP microarray data from 77 prostate cancer samples. While the two genes most frequently affected by genomic breakpoints were, as expected, ERG and TMPRSS2, surprisingly more known tumour suppressor genes (TSGs) than known oncogenes were identified at recurrent chromosome breakpoints. Certain well-characterised TSGs, including p53, PTEN, BRCA1 and BRCA2 are recurrently truncated as a result of chromosome rearrangements in prostate cancer. Interestingly, many of the genes residing at recurrent breakpoint sites have not yet been implicated in prostate carcinogenesis such as HOOK3, PPP2R2A and TCBA1. We have confirmed the generally reduced expression of selected genes in clinical samples using quantitative RT-PCR analysis. Subsequently, we further investigated the genes associated with the t(4:6) translocation in LNCaP cells and reveal the genomic fusion of SNX9 and putative TSG UNC5C, which led to the reduced expression of both genes. This study reveals another common mechanism that leads to the inactivation of TSGs in prostate cancer and the identification of multiple TSGs inactivated by chromosome rearrangements will lead to new direction of research for the molecular basis of prostate carcinogenesis.
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PMID:Chromosome rearrangement associated inactivation of tumour suppressor genes in prostate cancer. 2199 1