Molecular analysis of an unstable genomic region at chromosome band 11q23 reveals a disruption of the gene encoding the alpha2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) in human lymphoma.
A region of 150 kb has been analysed around a previously isolated, lymphoma associated, translocation breakpoint located at chromosome band 11q23. This balanced and reciprocal translocation, t(11;14)(q32;q23), has been shown to result in the fusion between chromosome 11 specific sequence and the switch gamma4 region of the IGH locus. The LPC gene, encoding a novel proprotein convertase belonging to the furin family, has been identified in this region. In order to characterize further the region surrounding the translocation, we have determined the detailed structure of LPC. Here we show that LPC consists of at least 16 exons covering 25 kb, and that there is a partial duplication, involving mobile genetic elements and containing LPC exons 13-17 in a tail-tail configuration at 65 kb downstream. Since the chromosomal breakpoint lay between these two structures, the intervening region was further analysed and shown to contain at least two unrelated genes. The previously known SM22 gene was localized close to the 3' tail of LPC. Furthermore, we identified the gene encoding the alpha2 subunit of platelet-activating factor acetylhydrolase (Pafah1a2) at the chromosomal breakpoint. The position of another previously identified breakpoint was also located to within the first intron of this gene. Altogether, our results give evidence of a genomic instability of this area of 11q23 and show that Pafah1a2 and not LPC is the gene disrupted by the translocation, suggesting that deregulated Pafah1a2 may have a role in lymphomagenesis.
Lecointe
N
N
ICRF, Department of Medical Oncology, Saint Bartholomew's Hospital Medical College, London, UK.
Meerabux
J
J
Ebihara
M
M
Hill
A
A
Young
B D
BD
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D020087:Alu Elements; D002880:Chromosomes, Human, Pair 11; D020440:Gene Duplication; D006801:Humans; D008223:Lymphoma / Q000235:genetics*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D010741:Phospholipases A / Q000235:genetics*; D018626:Retroelements; D012697:Serine Endopeptidases / Q000235:genetics*; D013381:Subtilisins
D008840:Microfilament Proteins; D009124:Muscle Proteins; D018626:Retroelements; C058992:Tagln protein, mouse; C051615:transgelin; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C099101:PCSK7 protein, human; C490930:Pcsk7 protein, mouse; D012697:Serine Endopeptidases; D013381:Subtilisins