Frequent joining of Bcl-2 to a JH6 gene in hepatitis C virus-associated t(14;18).
The t(14;18) chromosomal translocation, which joins the Bcl-2 proto-oncogene to an Ig J(H) gene, has increased prevalence in patients chronically infected with hepatitis C virus (HCV). We now establish a link between the molecular structure and clinical occurrence of HCV-associated t(14;18). A t(14;18) was detected by PCR in leukocytes from 22 of 46 HCV-infected patients (48%) and 11 of 54 healthy controls (20%) (p = 0.0053). Nucleotide sequence analysis of the Bcl-2/J(H) joins found a J(H)6 gene in 18 of 22 (82%) t(14;18) from HCV(+) patients, and 3 of 8 (38%) from controls (p = 0.031). The t(14;18) rarely contained J(H) gene mutations, or an intervening region sequence suggestive of D gene rearrangement or templated nucleotide insertion. Analysis of published t(14;18) nucleotide sequences established that the J(H)6 prevalence in t(14;18) from normal/nonneoplastic controls (48%) was significantly lower than in t(14;18) from our HCV(+) patients (p = 0.004) or from non-Hodgkin's lymphomas (66%, p = 0.003). We conclude that the increased prevalence of t(14;18) in HCV(+) patients occurs with a strong bias for Bcl-2/J(H)6 joins. In this regard, HCV-associated t(14;18) more closely resemble t(14;18) in lymphomas than t(14;18) from normal subjects.
Sasso
Eric H
EH
Department of Medicine, University of Washington, Seattle 98105, USA. eric.sasso@abbott.com
Martinez
Marina
M
Yarfitz
Stuart L
SL
Ghillani
Pascale
P
Musset
Lucile
L
Piette
Jean-Charles
JC
Cacoub
Patrice
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002908:Chronic Disease; D005260:Female; D006526:Hepatitis C / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2