Bio B11 Lec 20-21 C16 Proto-oncogenes, oncogenes, and tumor suppressor genes.
Proto-Onco genes: normal cell cycle controls genes. Onco gene: is
gene post mutation. Tumor suppressor gene: - Gene that controls protein that controls expression. - 1 copy of
the TSG is enough for it to take effect. - Must have 2 mutations to have control by mutation (mutation is
recessive). Fig 16-8: (a): Effects of mutations in tumor suppressor genes. Both copies of a TSG must be
knocked out to cause it to lose growth control. TSG's suffer loss-of-function mutations and/or epigenetic
inactivation that render them unable to restrain cell growth.
Fig 16-8 (b): Contrasting effects of mutations in Oncogenes. A
mutation in one of 2 copies (alleles) of an oncogene may be sufficient to cause a cell to lose growth control.
Oncogenes arise from proto-oncogenes as the result of gain-of-function mutations, that is, mutations that
cause the gene product to exhibit new functions that lead to malignancy.
In a normal hybrid, normal growth control is re-established
therefore malignant controls are overridden. Chromosome #1 = the largest, Chrom #23 = smallest. The region
deleted is between regions q11.21 & q21.2!
Mutations that arise in proto-oncogenes give rise to oncogene.
Inappropriate expression of normal protein: wrong: place/time/stage.
Translocon to bring in new regulatory region to control gene as chromosome segments are swapped.
A normal gene that encodes protein = the squiggly blue lines. --
changes protein in some way to alter function of protein. -- normal reg but many of the gene = higher
Fig 16-9: Activation of a proto-oncogene to an oncogene. Activation can be accomplished in several ways.
Pathway A: a mutation in the gene alters the structure and function of the encoded protein. In pathway B: gene
amplification results in over expression of the gene. Pathway C: a rearrangement of the DNA brings a new
DNA segment into the vicinity or up against the gene, altering either its expression or the structure of the
encoded protein. Region of chromosome 9 has gene BCR. With a reciprocal break,
part of chromosome 9 - chromosome 22. Part of chromosome 22 chromosome 9. (They swap) Creates Bck-
Abl fusion gene.
Systease 2 regions of these 2 genes prone to breakage.
*1: phosphorylates same targets for cell cycle to take place.
*2: in fusion gene no control elements thus regulated.
*3: thus cells constantly get signal telling them to divide.
Circus of Bcr-Abl = different stuff it interacts with. it interacts with
factors that promote cell cycle progression. it interacts with factors that disables programmed details, it alters
cell mobility and cell adhesion. By interacting with different partners it is transformed into a malignant state. Kill the cancer ... not the important stuff :/
You old = You have Cancer!
You should kind of be aware of this stuff... don't memorize it! Fig 16-10: Mutations in the RB gene that can lead to Retinoblastoma: (a): In sporadic cases of the disease, an
individual begins life with two normal copies of the RB gene in the zygote, and retinoblastoma occurs only in
those rare individuals in whom a given retina cell accumulates independent mutations in both alleles of the
(b): In familial (inherited) cases of the disease, an individual begins life with one banormal allele of the RB
gene, usually present as a deletion. Thus all the cells of the retina have at least one of their two RB genes non-
functional. If the other RB allele in a retinal cell becomes inactivated, usually as the result of a point mutation,
that cell gives rise to a retinal tumor.
Fig 16-11: The role of pRB in controlling transcription of genes required