Questions About Cancer? 1-800-4-CANCER
  • Print
  • email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Table 1. Genetic Diseases That Predispose to Osteosarcomaa

Syndrome  Description Location  Gene  Function 
Bloom syndrome [71]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.15q26.1BLM (RecQL3)DNA helicase
Diamond-Blackfan anemia [72]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 proteinsRibosome production [72,73]
Li-Fraumeni syndrome [74]Inherited mutation in TP53 gene. Affected family members at increased risk for bone tumors, breast cancer, leukemia, brain tumors, and sarcomas.17p13.1P53 DNA damage response
Paget disease [75]Excessive breakdown of bone with abnormal bone formation and remodeling, resulting in pain from weak, malformed bone.18q21-qa22LOH18CR1 IL-1/TNF signaling; RANK signaling pathway
Retinoblastoma [76]Malignant tumor of the retina. Approximately 66% diagnosed by age 2 years and 95% by age 3 years. Patients with heritable germ cell mutations at greater risk for subsequent neoplasms.13q14.2RB1 Cell-cycle checkpoint
Rothmund-Thomson syndrome [77,78]Also called poikiloderma congenitale. 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.8q24.3RTS (RecQL4)DNA helicase
Werner syndrome [79]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-p11.2WRN (RecQL2)DNA helicase; exonuclease activity

AML = acute myeloid leukemia; IL-1 = interleukin-1; MDS = myelodysplastic syndrome; TNF = tumor necrosis factor.
aTable adapted from Kansara and Thomas.[70]


  1. Kansara M, Thomas DM: Molecular pathogenesis of osteosarcoma. DNA Cell Biol 26 (1): 1-18, 2007.  [PUBMED Abstract]

  2. German J: Bloom's syndrome. XX. The first 100 cancers. Cancer Genet Cytogenet 93 (1): 100-6, 1997.  [PUBMED Abstract]

  3. Lipton JM, Federman N, Khabbaze Y, et al.: Osteogenic sarcoma associated with Diamond-Blackfan anemia: a report from the Diamond-Blackfan Anemia Registry. J Pediatr Hematol Oncol 23 (1): 39-44, 2001.  [PUBMED Abstract]

  4. Idol RA, Robledo S, Du HY, et al.: Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Blood Cells Mol Dis 39 (1): 35-43, 2007 Jul-Aug.  [PUBMED Abstract]

  5. Li FP, Fraumeni JF Jr, Mulvihill JJ, et al.: A cancer family syndrome in twenty-four kindreds. Cancer Res 48 (18): 5358-62, 1988.  [PUBMED Abstract]

  6. Grimer RJ, Cannon SR, Taminiau AM, et al.: Osteosarcoma over the age of forty. Eur J Cancer 39 (2): 157-63, 2003.  [PUBMED Abstract]

  7. Wong FL, Boice JD Jr, Abramson DH, et al.: Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk. JAMA 278 (15): 1262-7, 1997.  [PUBMED Abstract]

  8. Wang LL, Gannavarapu A, Kozinetz CA, et al.: Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst 95 (9): 669-74, 2003.  [PUBMED Abstract]

  9. Hicks MJ, Roth JR, Kozinetz CA, et al.: Clinicopathologic features of osteosarcoma in patients with Rothmund-Thomson syndrome. J Clin Oncol 25 (4): 370-5, 2007.  [PUBMED Abstract]

  10. Goto M, Miller RW, Ishikawa Y, et al.: Excess of rare cancers in Werner syndrome (adult progeria). Cancer Epidemiol Biomarkers Prev 5 (4): 239-46, 1996.  [PUBMED Abstract]