Chromosomal translocations involving immunoglobulin heavy chain (Igh) switch regions and an oncogene such as Myc represent initiating events in the development of many B cell malignancies. These translocations are widely thought to result from aberrant class-switch recombination. To test this model, we measured translocations in mice deficient in activation-induced cytidine deaminase (AID) that lack class-switch recombination. We found that AID made no measurable contribution to the generation of initial translocations, indicating that the intrinsic fragility of the switch regions or a pathway unrelated to AID is responsible for these translocations. In contrast, the outgrowth of translocation-positive cells was dependent on AID, raising the possibility that AID is important in tumor progression, perhaps by virtue of its mutagenic properties.
机构:
Cornell Univ, Weill Med Coll, Dept Med, Div Hematol & Oncol, Ithaca, NY 14853 USACornell Univ, Weill Med Coll, Dept Med, Div Hematol & Oncol, Ithaca, NY 14853 USA
Bergsagel, PL
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Kuehl, WM
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机构:Cornell Univ, Weill Med Coll, Dept Med, Div Hematol & Oncol, Ithaca, NY 14853 USA
机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Chaudhuri, J
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Tian, M
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机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Tian, M
;
Khuong, C
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机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Khuong, C
;
Chua, K
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机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Chua, K
;
Pinaud, E
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机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Pinaud, E
;
Alt, FW
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机构:
Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USAChildrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
机构:Harvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Chaudhuri, J
;
Alt, FW
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机构:
Harvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USAHarvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
机构:
Cornell Univ, Weill Med Coll, Dept Med, Div Hematol & Oncol, Ithaca, NY 14853 USACornell Univ, Weill Med Coll, Dept Med, Div Hematol & Oncol, Ithaca, NY 14853 USA
Bergsagel, PL
;
Kuehl, WM
论文数: 0引用数: 0
h-index: 0
机构:Cornell Univ, Weill Med Coll, Dept Med, Div Hematol & Oncol, Ithaca, NY 14853 USA
机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Chaudhuri, J
;
Tian, M
论文数: 0引用数: 0
h-index: 0
机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Tian, M
;
Khuong, C
论文数: 0引用数: 0
h-index: 0
机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Khuong, C
;
Chua, K
论文数: 0引用数: 0
h-index: 0
机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Chua, K
;
Pinaud, E
论文数: 0引用数: 0
h-index: 0
机构:Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Pinaud, E
;
Alt, FW
论文数: 0引用数: 0
h-index: 0
机构:
Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USAChildrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
机构:Harvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA
Chaudhuri, J
;
Alt, FW
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USAHarvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA