myc oncogene

c-myc is a protooncogene, the cellular homologue of a retroviral oncogene v-myc.

Like almost all retroviral oncogenes, the viral myc gene (v-myc) is derived from a cellular progenitor (c-myc).
v-myc was first defined in a group of avian retroviruses that cause myelocytic leukemia in chickens.

The myc locus maps to 8q24.12-q24.13

Sequences of the myc oncogene are highly evolutionarily conserved.

c-myc is expressed in proliferating cells in the body, such as keratinocytes, hepatocytes, bone marrow cells, fibroblasts, and vascular smooth muscle cells. It is repressed when these cells withdraw from the cell cycle.

• Induction of the transcription factor MYC promotes cell proliferation and transformation by activating growth-promoting genes, including ornithine decarboxylase-1 (ODC1) and CDC25A.
• MYC transcriptionally represses the expression of the growth arrest-specific-1 gene (GAS1).

Deregulated myc becomes an oncogene because it is sufficient to put cells into cycle and to keep them there.

myc deregulation is associated with various types of cancer - the type of tumor results from the combination of the particular oncogene with the time and place in which it is expressed.

myc becomes deregulated by a variety of different mechanisms:

• myc deregulation due to insertion of a v-myc oncogene by a retrovirus can lead to the formation of tumors in chickens, cats and rodents.
• myc can also be deregulated if a retrovirus inserts into the genome next to the c-myc gene and disrupts its normal control. This is the case in 18% of B lymphomas in chickens.
• myc can be deregulated if the region of the chromosome in which it resides is broken and translocated to a transcriptionally active region of the genome.

  Involvement of the myc oncogene in translocations is the prototype in the relationship between chromosomal abnormalities and oncogenes.
  Translocation is the reason for activation of myc in the human disease Burkitt's lymphoma, the commonest pediatric cancer in equatorial Africa and Papua New Guinea.
  The myc locus maps near the breakpoint that is translocated to chromosome 2, 14, or 22 in Burkitt lymphoma translocations.
  The c-myc gene is translocated to the immunoglobulin gene locus, which in is very active in the B lymphoid cells  which form the tumor.

Contrary to the previous belief that the myc gene is wildtype in Burkitt lymphoma, many of these tumors were found to exhibit at least one point mutation in myc predicted to lead to an amino acid substitution. A clustering of mutations can be observed in regions associated with transcriptional activation and apoptosis, and frequently occurred at sites of phosphorylation, suggesting that they had a pathogenetic role.     

• myc genes have been found to be amplified in various types of cancer; c-, N- and L- myc have all found to be amplified in small cell lung carcinoma, and N-myc is amplified in the most serious forms of childhood neuroblastoma.

      Amplification of myc can be observed in advanced widespread tumors and in aggressive primary tumors.