From OpenWetWare
Jump to navigationJump to search

CASE Complex Systems Biology Center

Home        Internal        Research        Publications        Lab Members        Contact       


Presenter: Jayant Avva

Date of Lecture: May 29, 2007

Scribe: Radina P. Soebiyanto

Date Posted by Scribe: May 30, 2007

Presentation Summary

Chapter 4 mainly focuses on oncogenes studies that arose because of the inability to find tumor viruses in the majority of human cancer (only two tumor viruses are found: human cervical carcinomas and hepatomas). The endogenous retrovirus (ERV) – whose genome is integrated in the germ-line chromosomes and subsequently carried by the daughter cells – were found to be incapable of infecting tumors and hence cannot form oncogenes. In fact, most of the ERVs are junk DNA in humans. The consensus for cancer to develop in humans is through carcinogens that transform normal genes to mutated genes.

In order to identify these mutated genes in the genome, researchers devised a novel technique called DNA transfection, where the DNA from chemically transformed cells are introduced into normal cells. This technique indicated that: (i) oncogenes can arise in the genomes of cells through a mechanism that is independent of tumor virus and (ii) the oncogenes in cell lines can act across species and tissue boundaries. The oncogenes discovered in human tumor cell lines through DNA transfection, are not only related to those carried by the retroviruses in animals (a table listing the retrovirus genes and their associated genes in human tumors was provided) but also derived from pre-existing normal cell genes.

There are three mechanisms for a proto-oncogene to become oncogene: (i) Deletion or point mutation in coding sequence, (ii) gene amplification and (iii) chromosome rearrangement. An example of a point mutation is the H-ras oncogene, where there is a mismatch in the ras gene sequence that causes different amino acids sequence to be encoded. In turn, this may result in a protein that has different structure from that of normal, as is the case of the constitutively active Epidermal Growth Factor Receptor (EGFR) protein in glioblastomas. Gene amplification simply refers to overproduction of normal protein. Chromosomal translocation indicates a fusion of a region from one chromosome to a non-homologous chromosome. Consequently, the resulting hybrid proteins are overproduced or hyperactive or both.

Discussion points and Questions

  • Whether junk DNA contributes to the cell function
  • Can junk DNA act as oncogene?
  • ERV exists in mice but not in human. However, most studies use DNA transfection technique in mice to investigate oncogenesis. How would this translate to human?
  • Slide 16: what does it mean by increased copy number
  • What does the clustering from micro array expression imply? The micro array data tells us which gene sequence to investigate further or that are involved in cancer.
  • There is a discussion on what it means by cell needs (slide 19). Do cells act for their own individual benefit, or is it for the good of the overall tissue or organ?
  • Can bacteria cause cancer?
  • Is it always single-point mutation or can it be multiple-point mutation?
  • In point mutation, how does the mutated gene get carried over to the daughter cells? If there is a mismatch occur in the sequence, would the mismatch repair mechanism in the daughter cells detect it?
  • What is Burkitt’s lymphoma?
  • Are glial cells only in the brain, or do they exist in the spinal cord as well?

An incomplete set of answers can be found in the following Word document