Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasmacytomagenesis provides a murine model to decipher progressive genetic events culminating in a B-cell neoplasia. Activation of the c-myc protooncogene by chromosomal translocation is considered an initiating event. Intracisternal A-type particles (IAPs) are defective retroviral-like structures present in the endoplasmic reticulum of plasmacytomas (PCTs). IAP proviral insertions have been documented to engender negative or positive effects on the expression of nearby cellular genes. We have isolated a gene, PANG (plasmacytoma-associated neuronal glycoprotein), that is ectopically transcribed in a number of PCTs due to IAP long terminal repeat (LTR) activation. A full-length PANG cDNA was isolated from an MPC-11 plasma cell tumor cDNA library and encodes a polypeptide of about 113 kDa with six immunoglobulin C2-like and four type III fibronectin-like domains. PANG bears a striking resemblance to axonal glycoproteins TAG-1 and F11 known to function in neuronal outgrowth. An extensive survey revealed a predominant 3.6-kb PANG transcript in 60% (30 of 50) of PCTs as well as unique smaller and larger species. All other normal and transformed lymphoid and nonlymphoid cell lines and normal tissues were negative for PANG expression except for the brain, wherein unique 4.0- and 6.1-kb transcripts were detected. Reverse transcriptase PCR analysis revealed IAP LTR fusion to PANG mRNAs in five PCTs and in a neuroblastoma line. The 5' end of a mouse brain PANG cDNA was identical to the MPC-11 PANG transcript except for the precise replacement of its 5' LTR sequence.
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PMID:PANG, a gene encoding a neuronal glycoprotein, is ectopically activated by intracisternal A-type particle long terminal repeats in murine plasmacytomas. 810 13

We describe the molecular analysis of chromosomal rearrangements in familial t(3;6)(p12.3;q24.3) and t(3;12)(q13.13;q24.23) associated with the development of conventional renal cell carcinomas (RCC). We mapped the breakpoints by high-density oligo array comparative genomic hybridization of tumor cells in t(3;6) at chromosome 3p12.3 between PDZRN3 and CNTN3; the chromosomal rearrangement at 6q24.3 was mapped within the seventh intron of the STXBP5 gene. In the second case, the break at 3q13.13 was mapped downstream of PVRL3 and the breakpoint at 12q24.23 between HSPB8 and CCDC60, one allele of the latter being deleted. Reverse transcriptase polymerase chain reaction analysis of the PDZRN3, CNTN3, STXBP5, PVRL3, HSPB8, and CCDC60 genes revealed slight variation in the copy number of transcripts, but without correlation to the chromosomal rearrangements in translocation-associated and sporadic conventional RCCs. Loss of heterozygosity at chromosome 3p and mutation of VHL occurred at the same frequency in both familial and sporadic cases. Based on our model of nonhomologous chromatid exchange and the data on molecular studies, we suggest that the germline translocation serves as a rate-limiting step toward tumor development by generating a high number of cells with loss of the derivative chromosome carrying the 3p segment.
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PMID:Molecular analysis of germline t(3;6) and t(3;12) associated with conventional renal cell carcinomas indicates their rate-limiting role and supports the three-hit model of carcinogenesis. 2063 63