• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Insertion of c-Myc into Igh induces B-cell and plasma-cell neoplasms in mice.

We used gene targeting in mice to insert a His(6)-tagged mouse c-Myc cDNA, Myc(His), head to head into the mouse immunoglobulin heavy-chain locus, Igh, just 5' of the intronic enhancer, Emu. The insertion of Myc(His) mimicked both the human t(8;14)(q24;q32) translocation that results in the activation of MYC in human endemic Burkitt lymphomas and the homologous mouse T(12;15) translocation that deregulates Myc in certain mouse plasmacytomas. Beginning at the age of 6 months, Myc(His) transgenic mice developed B-cell and plasma neoplasms, such as IgM(+) lymphoblastic B-cell lymphomas, Bcl-6(+) diffuse large B-cell lymphomas, and CD138(+) plasmacytomas, with an overall incidence of 68% by 21 months. Molecular studies of lymphoblastic B-cell lymphoma, the most prevalent neoplasm (50% of all tumors), showed that the lymphomas were clonal, overexpressed Myc(His), and exhibited the P2 to P1 promoter shift in Myc expression, a hallmark of MYC/Myc deregulation in human endemic Burkitt lymphoma and mouse plasmacytoma. Only 1 (6.3%) of 16 lymphoblastic B-cell lymphomas contained a BL-typical point mutation in the amino-terminal transactivation domain of Myc(His), suggesting that most of these tumors are derived from naive, pregerminal center B cells. Twelve (46%) of 26 lymphoblastic B-cell lymphomas exhibited changes in the p19(Arf)-Mdm2-p53 tumor suppressor axis, an important pathway for Myc-dependent apoptosis. We conclude that Myc(His) insertion into Igh predictably induces B-cell and plasma-cell tumors in mice, providing a valuable mouse model for understanding the transformation-inducing consequences of the MYC/Myc-activating endemic Burkitt lymphoma t(8;14)/plasmacytoma T(12;15) translocation.

Pubmed ID: 15735016

Authors

  • Park SS
  • Kim JS
  • Tessarollo L
  • Owens JD
  • Peng L
  • Han SS
  • Tae Chung S
  • Torrey TA
  • Cheung WC
  • Polakiewicz RD
  • McNeil N
  • Ried T
  • Mushinski JF
  • Morse HC
  • Janz S

Journal

Cancer research

Publication Data

February 15, 2005

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes
  • Burkitt Lymphoma
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 8
  • Disease Models, Animal
  • Genes, Tumor Suppressor
  • Genes, myc
  • Humans
  • Immunoglobulin Heavy Chains
  • Lymphoma, B-Cell
  • Mice
  • Molecular Sequence Data
  • Plasmacytoma
  • Point Mutation
  • Precancerous Conditions
  • Promoter Regions, Genetic
  • Transgenes
  • Translocation, Genetic