From: Childhood Cancer Genomics (PDQ®)
PDQ Cancer Information Summaries [Internet].
Bethesda (MD): National Cancer Institute (US); 2002-.
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Table 1. Genetic Diseases That Predispose to Osteosarcomaa
| Syndrome | Description | Location | Gene | Function |
|---|---|---|---|---|
| Bloom syndrome [8] | Rare inherited disorder characterized by short stature and sun-sensitive skin changes. Often presents with a long, narrow face, small lower jaw, large nose, and prominent ears. | 15q26.1 | BLM (RecQL3) | DNA helicase |
| Diamond-Blackfan anemia [9] | Inherited pure red cell aplasia. Patients at risk for MDS and AML. Associated with skeletal abnormalities, such as abnormal facial features (flat nasal bridge, widely spaced eyes). | Ribosomal proteins | Ribosome production [9,10] | |
| Li-Fraumeni syndrome [11] | Inherited mutation in TP53 gene. Affected family members at increased risk for bone tumors, breast cancer, leukemia, brain tumors, and sarcomas. | 17p13.1 | P53 | DNA damage response |
| Paget disease [12] | Excessive breakdown of bone with abnormal bone formation and remodeling, resulting in pain from weak, malformed bone. | 18q21-qa22 | LOH18CR1 | IL-1/TNF signaling; RANK signaling pathway |
| 5q31 | ||||
| 5q35-qter | ||||
| Retinoblastoma [13] | Malignant tumor of the retina. Approximately 66% of patients diagnosed by age 2 years and 95% of patients by age 3 years. Patients with heritable germ cell mutations at greater risk for subsequent neoplasms. | 13q14.2 | RB1 | Cell-cycle checkpoint |
| Rothmund-Thomson syndrome (also called poikiloderma congenitale) [14,15] | Autosomal recessive condition. Associated with skin findings (atrophy, telangiectasias, pigmentation), sparse hair, cataracts, small stature, and skeletal abnormalities. Increased incidence of osteosarcoma at a younger age. | 8q24.3 | RTS (RecQL4) | DNA helicase |
| Werner syndrome [16] | Patients often have short stature and in their early twenties, develop signs of aging, including graying of hair and hardening of skin. Other aging problems such as cataracts, skin ulcers, and atherosclerosis develop later. | 8p12-p11.2 | WRN (RecQL2) | DNA helicase; exonuclease activity |
AML = acute myeloid leukemia; IL-1 = interleukin-1; MDS = myelodysplastic syndrome; RANK = receptor activator of nuclear factor kappaB ligand; TNF = tumor necrosis factor.
aTable adapted from Kansara et al.[7]