cancer- tumor supressor genes

tumor suppression genes

Tumor Suppressor genes – loss of function of these types of genes leads
to an increase in proliferation, once the intact/WT versions of these genes are introduced to the cell, the cell’s ability to form tumors is lost (return to normal phenotype

unilateral (sporadic)

Two somatic mutations need to occur
• This is extremely unlikely!

bilateral (familial)

mutant allele is already present due to germ line transmission
• Only one somatic mutation needs to occur in retinal precursor cells for disease development

i hybrid cells tumorigenic

Cancer cells derived from viral-induced tumors

hybrid cells non tumorigenic

Cancer cells derived from most kinds of non-virus-induced human tumors

LOH = Loss of heterozygosity

LOH = loss of heterozygosity
• More probable way of eliminating the normal allele compared to a second mutation in the same gene
• Cells that are proliferating are going to go through these processes often
• Example below – LOH achieved via mitotic recombination

Hemizygosity = LOH

Hemizygosity = LOH can occur by simply breaking off and discarding an entire chromosomal region without replacing it with
a copy from the other homologous chromosome

LOH can occur through the mis-segregation of chromosomes during mitosis = mitotic nondisjunction

Best understood heritable colon cancer syndrome

Adenomatous
polyposis coli (APC) – called familial adenomatous polyposis (FAP)
• Inherited susceptibility to develop adenomatous (non-cancerous) polyps in
the colon
• Polyps are benign but are prone to develop into carcinomas
• 1% of all colon cancers
Colon from FAP patient Normal Colon

Epithelial cells in the gastrointestinaltract

enterocytes

APC

product of the adenomatous
polyposis gene – negatively controls the
levels of β-catenin in the cytosol

Von Hippel-Lindau syndrome

= hereditary predisposition to the
development of a variety of tumors, including carcinomas of the kidney,
tumors of the adrenal gland, and blood vessel tumors of the central
nervous system and retina

normoxia

normal oxygen levels

hypoxia

abnormal oxygen levels

angiogenesis

formation of new
blood vessels – VEGF – attracts and
stimulates the growth of endothelial
cells needed to form new blood
vessels