The absolute number of trans-rearrangements between the TCRG and TCRB loci is predictive of lymphoma risk: a severe combined immune deficiency (SCID) murine model.
Pilot studies in human populations have demonstrated a correlation between the level of antigen receptor trans-rearrangements and risk (at the population level) of lymphoid malignancy. Irradiation of newborn severe combined immune deficiency mice results in an increased risk of subsequent development of thymic lymphoma (100% of mice so irradiated are dead of thymic lymphoma by 20 weeks of age). We, therefore, assayed the occurrence of trans-rearrangements in this well-controlled mouse mutant system and found a 50-100-fold increase in the absolute number of TCRGV-TCRBJ trans-rearrangements compared to unirradiated littermates (and a comparable fold increase over age-matched BALB/c mice) at 2 weeks following irradiation. We also found a marked disproportion in generating trans-rearrangements versus intralocus rearrangements in the severe combined immune deficiency system compared to BALB/c, independent of irradiation. The trans-rearrangements noted were polyclonal in nature. These data, again, suggest that the absolute level of antigen receptor trans-rearrangements may serve as a biomarker of lymphoma risk.
Lista
F
F
Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20889, USA.
Bertness
V
V
Guidos
C J
CJ
Danska
J S
JS
Kirsch
I R
IR
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D008223:Lymphoma / Q000209:etiology / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012306:Risk; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics; D045567:VDJ Recombinases
D015415:Biomarkers; D011948:Receptors, Antigen, T-Cell; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases