Tp53 deletion in B lineage cells predisposes mice to lymphomas with oncogenic translocations
30.05.2011
Rowh MA, Demicco A, Horowitz JE, Yin B, Yang-Iott KS, Fusello AM, Hobeika E, Reth M, Bassing CH
Oncogene. 2011; 30(47):4757-64
Developing B lymphocytes assemble and diversify their immunoglobulin (Ig) genes via RAG/AID-initiated genomic rearrangements and mutations that involve the induction of DNA double strand breaks (DSBs). These DSB are repaired by the non-homologous end-joining pathway. In the case the repair fails the open DNA end are recognized by the p53 pathway and the cells are send into apoptosis. In the case this control does not work genomic unstable B cells accumulate chromosomal translocations that can result in deregulated gene products and the development of lymphomas. By preventing potentially oncogenic translocations p53 acts as a tumor suppressor. We have used the mb1Cre mouse line displaying a B cell specific Cre activity and mice with a floxed p53 gene to analyses the function of p53 specifically in B cells of the mouse. All mb1Cre x p53fl/fl mice succumbed to lymphoid tumors containing Ig gene rearrangements. Most B cell tumors in these mice harbored oncogenic translocations including Igh/c-myc. Our data indicate that p53 prevents transformation of B cells caused by RAG/AID-initiated DSB intermediates and oncogenic translocations.
