3. Proto oncogenes are normal genes involved in
the cell growth and division.
Mutation to a proto oncogene can lead to it to
become a cancer-causing oncogene by
producing growth stimulating protein that are in
excess level.
A tumour suppressor gene or anti oncogene is a
gene that protect a cell from path to cancer.
When this gene is mutated to cause a loss or
reduction in its function, the cell can progress
to cancer.
INTRODUCTION
4. An oncogene formed by mechanism encodes an
onco protein.
Oncogene, that are slightly differs from the
normal protein encoded by the corresponding
proto oncogene.
Normally the oncogenes are not expressed.
They arise, the gain of function mutations that
convert proto oncogene to oncogene and act
dominantly.
Mutation is only one of the two alleles is sufficient
for induction of cancer.
5.
6.
7. HOW DOSE A PROTO ONCOGENE BECOME AN
ONCOGENE ?
Due to different type of DNA alteration.
It is classified into two broad categories,
Point mutation Chromosomal
Rearrangement
8. 1.POINT MUTATION
To the substitution of one base for another,
resulting in a change in that particular amino
acids.
Commonly produce a protein that has lost its
ability to the regulating by external signalling.
In point mutation translate into a changed amino
acid that has different biochemical properties
than the amino acid the DNA sequence originally
encoded for.
This change in amino acid can mimic
phosphorylation or inhibit binding of negative
regulatory molecules, resulting in a constituently
active protein.
9. 2.CHROMOSOMAL
REARRANGEMENT/TRANSLOCATION
It produce oncogene in several way
I. Fusion of one chromosome to another, result
in a strong promoter being placed upstream of a
gene that would normally be either absent or
present in very low quality.
The effect of increasing the intracellular
concentration.
II. By fusion protein, or proteins that are the
product of two separate gene that have been
joined.
10. ALTERATIONS CHANGING PROTO
ONCOGENE INTO ONCOGENE
The alterations distinguishing oncogenes from proto
oncogene fall into several clearly defined classes
involving:
1 Sequence substitution in the gene/coding or its
control region.
2 Onco gene created by deletions.
3 Translocations and oncogene formation.
4 Amplification in oncogene production.
11. SEQUENCE SUBSTITUTION IN THE
GENE/CODING OR ITS CONTROL REGION
Mutation altering coding segments, promoter or
enhancer are among the most common alterations
Eg:Oncogene forms the ras gene associated with
human bladder carcinoma ras gene.
The alteration cause amino acid substitution in
corresponding position in the G protein
encoded in the gene.
12. Mutation leads to substitution of valine of
glycine at position 12 in the amino acid
sequence of the encoded or protein.
Eg:Human lung cancer ras gene.
Leucine for glutamine at position 61 in the
encoded G protein.
13. ONCOGENE CREATED BY DELETION
Deletion of sequences from either control or
coding regions eg: myc gene
Three exon separated by two introns .Its
oncogenic form, first exon and intron and the
control sequences in advance of the gene are
missing .
Deletion of first exon, which is normally copied
into the myc mRNA but not translated into a
protein sequence, may alter RNA processing to
increase the amount of mRNA available to
ribosomes in the cytoplasm .
Removal of the promoter region of the myc gene
does not prevent transcription .
14. TRNSLOCATION AND ONCOGENE FORMATION
Translocation of gene to a new position in the
chromosomes often places the gene in a control
environment that is distinctly different from its
previous location , may be absent in the new
environment causing them to be more active.
The gene in its new location become more active by
influence of highly active promoter or enhancer of
another gene.
This translocation may result in uncontrolled cell
division.
15. Many translocation responsible for gene
movement, result of gross exchanger in which
whole chromosome segment separate.
Some translocation brakes occur in two
chromosomes, setting up a reciprocal exchange
between chromosome involved
eg:1 Leukaemia
2 Burkitt’s lymphoma
Reciprocal exchange of
chromosome 8 and 14
16. AMPLIFICATION IN ONCOGENE PRODUCTION
Gene amplification results from over replication
of restricted segments of the DNA.
The long chromosomes of eukaryotic cells
contain multiple sites from which DNA
replication of a sub part of the DNA molecule
known as replicon.
17. Normally each replicon is activated only once
during an S period. So that the entire DNA
molecule is duplicated only once .
Rarely one or more replicons may be activated
more than one during an S phase causing
amplification, leading to cancer.
18.
19.
20. ONCOGENE FORMATION WITHOUT
ALTERATION IN GENE SEQUENCES
In some instance normal genes are converted to
oncogenes without changes in the coding or
control sequence of the gene itself .
This process term insertional activation.
