1.
2.
------------------------------
Modifiable Risk factors
Socio economic status
Radiation exposure
DNA damage
Mutation in the RB1 gene
Altered p53 Function
pRB remains hypophosphorylated
and bound to E2F
Suppressor
of
multipotent
progenitor
cells
Cycle stops in G1 phase
Absence of cell cycle arrest
Genomic
instability and
uncontrolled
proliferation
of MSC`s
Non-Modifiable Risk factors
Age
2. Sex
3. Height
Genetics (Retinoblastoma, Rothmund-Thomson Syndrome)
Non-cancerous bone diseases (Paget`s disease of the bone,
Genetic multiple osteochondroma, Fibrous dysplasia)
Ectopic SFRP2
overexpression in
normal osteoblast
precursors
Mutation in the TP53 gene
Absence of mitogenic stimuli
1.
2.
3.
Deregulation
of the activity
of immune
MSC`s
Degradation of DNA methylation
process
Increased
stochastic
variation in
gene
expression
Suppression of normal
osteoblast
differentiation
Start of tight
regulation of
histone
modifications
Oncogenesis
Genomic instability
Inhibition of apoptosis
Prevent the repair of DNA damage
Genomic instability
Further
mutation
Uncontrolled cell growth
Transpoon
element
reactivation
and
remobilization
Cytoplasmic
chromatin
segment
Gene
dysregulation
Disrupted Homeostasis and regeneration
Tumor development
Release of cytokine
Interleukin 6 activates Janus
kinase
Phosphorylation of
transcription activator 3
Increased cell proliferation.
Inhibits apoptosis of the
MSC`s and OS-derived cells
Transforming growth factor
beta enhance the migration
potential of OS cells
Tumor necrosis factor
maintain tumor cells in
undifferentiated state
Interleukin 34 stimulate
growth and survival of
myeloid cells
Macrophage proliferation to
the profile of M2 tumorassociated macrophages
Activation of pleiotropic
functions involved in
regulating cell proliferation
and differentiation,
apoptosis, cell migration and
invasion, extracellular matrix
production, angiogenesis
and immune response
Tumor progression
Interleukin 17 induces
angiogenesis stimulators
including VEGF
Angiogenesis
Redness
Hypermethylation of
the RASSF1A
Hypomethylation of
the 1RX1 gene
Overexpression of the
MPM2 gene
Activation of the cMc
and P13/Akl signaling
pathways
Increased p53
degradation
Reduction in the
production of P16INK4a
Overexpression
of CD4 and
inactivation of
PRB
Suppression of the
GADD45 gene
encoding the 5-hmc
production
Absence of DNA repair
Increase in
Mdm2 levels
Degradation of
p53
Impede demethylation
of other genes
Uncontrolled cell cycle
Supression of
the P14ARF
Apoptosis Inhibition
Increase in the rate, growth, and proliferation of cancer cells
Aggressive growth/malignancy
Anaplastic tumor cells produce osteoid and callus
Deposition of osteoid
Infiltration of the normal compact bone
Destruction of the normal compact bone
Bone fracture
Replacement by masses of osteoid
Impregnation of the cortex
Lifting of the periosteum
Formation of a soft tissue mass
Periosteal reaction
Redness, swelling, pain
Codman Triangle
Presence of lump
Development of Malignant osteoblasts
Increase in alkaline phosphatase levels
Escape of cancer from primary tumor
Travel within the circulation system and colonization
Establishment of metastatic lesions in the lungs
Poor prognosis
Cough
Dyspnea
Chest pain