C-myc translocations

Rodig SJ, Rutok IL, Paterson IC et al (2010) The pre-B-cell receptor associated protein VpreBS is a useful diagnostic marker for identifying c-MYC translocated lymphomas. Haematologica 95 2056-2062... 

AID-induced c-myc translocation, miR-155 acts as a tumor suppressor microRNA [335, 336]. The promoter gene of miR-124-1 in chromosome 8p is frequently methylated (silenced) in human malignant lymphoma cells, including those of NK/T lymphoma cells. The miR-124-2 is a direct inhibitor of the CDK6 cyclin-dependent kinase mRNA [337]. Moderate and pronounced anti-AID mRNA activity is exerted by miR-155 and miR-93, respectively [338]. 

Fig. 11.4. Model of signal transduction via the IL-2 receptor. Binding of IL-2 to the IL-2 receptor initiates activation of the Janus kinases Jakl and Jak3. These phosphorylate tyrosine residues in the P-chain of the IL-2 receptor and in the transcription factor StatS. SH2 domains or PTB domains of adaptor proteins can bind to the Tyr phosphate residues of the P-chain and, as shown in the figure for the Shc/Grb2/Sos complex, can transmit a signal in the direction of the Ras pathway. The phosphorylated transcription factor StatS is translocated into the nucleus and activates the transcription of corresponding gene sections. Another signaling pathway starting from the activated IL-2 receptor involves the Lck and Syk tyrosine kinases (see Chapter 8). The pathway leads to induction of genes for transcription factors such as c-Myc and c-Fos.

The c-myc gene is presented as an example of overexpression of a transcription factor due to translocation. 

Translocation associated with Burkitt s lymphoma. The protooncogene c-myc, on the end of chromosome 8q, is translocated to the end of chromosome 14q, adjacent to the immunoglobulin constant gene, Ig-CfJL. (From J. Yunis, The chromosomal basis of human neoplasia. Science 221 227-236, Jan. 1, 1983. Copyright 1983 by the AAAS. Reprinted by permission.)... 

Qin Z. H., Chen R. W., Wang Y., Nakai M., Chuang D. M., and Chase T. N. (1999). Nuclear factor kB nuclear translocation upregulates c-Myc and p53 expression during NMDA receptor-mediated apoptosis in rat striatum. J. Neurosci. 19 4023 1033. 

Figure 24.18. Translocation of c-myc in Burkitt s lymphoma. c-Myc is translocated to an immunoglobulin region on either chromosome 22,14, or 2, and its expression is now under the regulation of the immunoglobulin promoter.

PNA Translocated c-Myc (Ep,) enhancer Cell culture (Endogenous gene) Burkitt s Lymphoma (11)... 

Cutrona G, Carpaneto EM, Ponzanelli A, Ulivi M, Millo E, Scarfi S, Roncella S, Benatti U, Boffa LC, Eerrarini M. Inhibition of the translocated c-myc in Burkitt s lymphoma by a PNA complementary to the E mu enhancer. Cancer Res. 2003 63 6144-6148. 

The c-myc gene is the proto-oncogene of avian myelocytoma virus. It binds to DNA and is involved in transcription regulation. The gene product, p62, is located in the nucleus of transformed cells, and levels of c-myc correlate with the rate of cell division. The c-myc protein is essential for DNA replication and enhances mRNA transcription. Activation of the c-myc gene is associated with B- and T-ceH lymphoma, sarcomas, and endotheliomas. In leukemias and lymphomas, increased c-myc expression may be due to amplification or chromosomal translocation of the gene. In acute T-celi leukemias, there is an (8 14) (q24 qll) translocation that... 

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