Abstract
B-cell lymphomas arising in lymph nodes and spleen of aging mice deficient in the Ung DNA glycosylase were recovered, dispersed, grown in short-term culture, and CD19-positive B-cells retrieved and analysed. Several tumors as well as controls only expressed detectable amounts of the Aid deaminase after mitogenic stimulation, as estimated by real-time PCR of transcripts. However, one unusually large lymph node tumor expressed a high level of Aid constitutively. This particular tumor also showed a substantially increased mutation frequency in the Aid gene itself as well as in the bcl-6 and c-myc genes, but not in the p53 gene, consistent with aberrant somatic hypermutation. Other B-cell lymphomas from Ung−/− mice exhibited a modest increase in mutation frequency.
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References
Barnes DE and Lindahl T . (2004). Annu. Rev. Genet., 38, 445–476.
Coleman AE, Ried T and Janz S . (2000). Genes Chr. Cancer, 29, 70–74.
Gearhart PJ . (2003). Oncogene, 22, 5379–5380.
Imai K, Slupphaug G, Lee WI, Revy P, Nonoyama S, Catalan N, Yel L, Forveille M, Kavli B, Krokan HE, Ochs HD, Fischer A and Durandy A . (2003). Nat. Immunol., 4, 1023–1028.
Martin A and Scharff MD . (2002). Proc. Natl. Acad. Sci. USA, 99, 12304–12308.
Muramatsu M, Kinoshita K, Fagarasan S, Tamada S, Shinkai Y and Honjo T . (2000). Cell, 102, 553–563.
Nilsen H, Rosewell I, Robins P, Skjelbred F, Andersen S, Slupphaug G, Daly G, Krokan HE, Lindahl T and Barnes DE . (2000). Mol. Cell, 5, 1059–1065.
Nilsen H, Stamp G, Andersen S, Hrivnak G, Krokan HE, Lindahl T and Barnes DE . (2003). Oncogene, 22, 5381–5386.
Okazaki IM, Hiai H, Kakazu N, Yamada S, Muramatsu M, Kinoshita K and Honjo T . (2003). J. Exp. Med., 197, 1173–1181.
Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RSK, Küppers R and Dalla-Favera R . (2001). Nature, 412, 341–346.
Pasqualucci L, Guglielmino R, Houldsworth J, Mohr J, Aoufouchi S, Polakiewicz R, Chaganti RSK and Dalla-Favera R . (2004). Blood, 104, 3318–3325.
Rada C, di Noia J and Neuberger MS . (2004). Mol. Cell, 16, 163–171.
Rada C, Williams GT, Nilsen H, Barnes DE, Lindahl T and Neuberger MS . (2002). Curr. Biol., 12, 1748–1755.
Revy P, Muto T, Levy Y, Geissman F, Plebani A, Sanai O, Catalan N, Forveille M, Duforque-Lagelouse R, Gennery A, Tezcan I, Ersoy F, Kayserilli H, Ugazio AG, Brousse N, Muramatsu M, Notarangelo LD, Kinoshita K, Honjo T, Fischer A and Durandy A . (2000). Cell, 102, 565–575.
Rogozin IB and Kolchanov NA . (1992). Biochim. Biophys. Acta, 1171, 11–18.
Acknowledgements
We thank Ashfaq Gilkar and Gordon Stamp for histopathology, Paul AW Edwards and Mira Grigorova for help with spectral karyotyping, and Geza Hrivnak and Del Watling for tumor collection. This work was supported by Cancer Research UK.
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Nilsen, H., An, Q. & Lindahl, T. Mutation frequencies and AID activation state in B-cell lymphomas from Ung-deficient mice. Oncogene 24, 3063–3066 (2005). https://doi.org/10.1038/sj.onc.1208480
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DOI: https://doi.org/10.1038/sj.onc.1208480
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