Array Comparative Genomic Hybridization in Osteosarcoma

  • Bekim Sadikovic
  • Paul C. Park
  • Shamini Selvarajah
  • Maria Zielenska
Part of the Methods in Molecular Biology book series (MIMB, volume 973)


Osteosarcoma, the most frequent primary bone tumor, is a malignant mesenchymal sarcoma with a peak incidence in young children and adolescents. Left untreated, it progresses relentlessly to local and systemic disease, ultimately leading to death within months. Genomically, osteosarcomas are aneuploid with chaotic karyotypes, lacking the pathognomonic genetic rearrangements characteristic of most sarcomas. The familial genetics of osteosarcoma helped in elucidating some of the etiological molecular disruptions, such as the tumor suppressor genes RB1 in retinoblastoma and TP53 in Li–Fraumeni, and RECQL4 involved in DNA repair/replication in Rothmund–Thomson syndrome. Genomic profiling approaches such as array comparative genomic hybridization (aCGH) have provided additional insights concerning the mechanisms responsible for generating complex osteosarcoma genomes. This chapter provides a brief introduction to the clinical features of conventional osteosarcoma, the predominant subtypes, and a general overview of materials and analytical methods of osteosarcoma aCGH, followed by a more detailed literature overview of aCGH studies and a discussion of emerging genes, molecular mechanisms, and their clinical implications, as well as more recent application of integrative genomics in osteosarcoma. aCHG is helping elucidate genomic events leading to tumor development and evolution as well as identification of prognostic markers and therapeutic targets in osteosarcoma.

Key words

Osteosarcoma aCGH Array comparative genomic hybridization Copy number RUNX2 Genomic instability Genomic integration Integrative analysis 



B.S. was a past recipient of the National Cancer Institute of Canada (currently Canadian Cancer Society) and the Terry Fox Foundation Fellowship in osteosarcoma research. S.S. was a past recipient of the Canadian Institute of Health Research Fellowship for Graduate Training in Molecular Medicine. M.Z is funded by the Canadian Cancer Society grant CCRI-020247.


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Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Bekim Sadikovic
    • 1
  • Paul C. Park
    • 2
  • Shamini Selvarajah
    • 3
  • Maria Zielenska
    • 4
  1. 1.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  2. 2.Department of Pathology and Molecular MedicineQueens UniversityKingstonCanada
  3. 3.Department of Medical OncologyDana-Farber Cancer Institute, Harvard Medical SchoolBostonUSA
  4. 4.Department of Laboratory Medicine and PathobiologyThe Hospital for Sick ChildrenTorontoCanada

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