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Home > Disclaimer > Osteosarcoma

Most patients have no known causes or risk factors, however there are some known associations:

1. Ionizing radiation is a known risk but is implicated in <3% of cases.

2. Pre-existing Benign lesions

• 2% of patients with Paget’s disease develop ostesarcoma later in life, and these patients do very poorly.
• Osteochondromas, enchondromas and fibrous dysplasia can all give arise to osteosarcoma, but this is very rare, chondrosarcomatous degeneration being more common.

3. Genetic syndromes associated with defects in cell function.

 

Genetic Syndromes Associated with osteogenic sarcoma:

Syndrome	Description
Li Fraumeni	Rare inherited disorder affecting p53.   Also have an increased risk of breast cancer, CNS tumors, soft tissue sarcoma and adrenocortical carcinoma   3-5% of children diagnosed with osteoasrcoma will have a germ line p53 mutation.
Bilateral retinoblastoma	Develop bilateral retinoblastoma, due to a defect in the Rb gene.   Follows Knudson’s two-hit hypothesis for tumour suppressor genes   Relative risk for developing osteosarcoma is 300 - 500 times - but much greater in areas that have previously received radiation therapy (RT).
Rothmund Thompson syndrome	Autosomal recessive inheritance   Small stature, skeletal dysplasia and cataracts   High risk for osteosarcoma   Mutation in the RECQL4 gene, which encodes a DNA helicase.

 

Molecular Mechanisms

Osteosarcomas are cytogenetically highly disrupted tumours with multiple cellular processes involved. Nonetheless, two mechanisms have been quite well established.

p53

Tumour-suppressor gene located at 17p13.1.

Commonly disrupted in osteosarcoma; p53 deficient mice develop osteosarcomas.

Involved in multiple cell processes that control growth and replication as well DNA damage detection and repair and apoptosis. Loss of this central regulator seems important for tumour development

Rb

The gene for retinoblastoma protein is found at 13q14.2  and is associated with osteosarcoma (with or without a prior history of retinoblastoma).

Osteosarcomas show Rb gene deletions and rearrangements, altered mRNA expression levels and abnormal retinoblastoma proteins.

Non-germ line mutations of p53 and Rb occur in osteosarcoma

 

External Link: Syndromes associated with osteosarcoma at the National Cancer Institute

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