Malignancy means that the mass has uncontrolled growth and has the ability
to invade neighboring tissues or spreading to distant sites
Tumors that do not metastasize are not cancerous but are called benign
tumors
Oncogenes
Mutations in oncogenes
Examples of oncogenes :
1. Ras GTPase
Most common mutation is to lose the GTPase activity, and Ras will remain
bound with GTP, which will cause a tumor.
Loss of extracellular domain, which will allow it to dimerize without any
ligand, which will also cause a tumor.
Translocation breakpoints are within the introns of two genes, thereby fusing
two genes into one abnormal gene
The oncogene encodes a chimeric (from 2 genes) protein with novel (new)
oncogenic properties
Philadelphia chromosome
The juxtaposition of BCR sequences and ABL sequences allows the synthesis
of a chimeric protein that is longer than the normal Abl protein and has
increased tyrosine kinase activity.
A new drug Imatinib has been developed that inhibits enhanced tyrosine
kinase activity monoclonal antibodies that bind to the receptor, and
prevents the binding of GF, and locks the receptor in an inactive
conformation, which will inhibit the signaling pathway.
Burkitt lymphoma
B-cell tumor of the jaw commonly seen in equatorial Africa but rare elsewhere
Telomerase as an oncogene
After hundreds of cell divisions, the chromosome ends will become damaged.
DNA damage causes cells to stop dividing and enter G0 of the cell cycle and
ultimately undergo apoptosis
But when they looked at family pedigrees and looked at tumors that are
caused by mutations in gene suppressors , they found that they are passed in
an Autosomal Dominant manner This made them come up with what is
called the 2 hits origin captor
Linkage mapping
A linkage map is a genetic map that shows the position of genes relative to
each other in terms of recombination frequency
Genes whose loci are nearer to each other are less likely to be separated onto
different chromatids during crossover.
Lets assume that we have one pair of homologous chromosomes: one from
-Lets assume the gene of the bristle length = s
the father and the other from the mother.
where :
s+ allele of the long bristle.(dominant)
s allele of the short bristle.
- and the gene of the body color = e where:
e+ allele of gray color. (dominant)
e allele of white color.