Osteosarcomas With Few Chromosomal Alterations or Adult Onset Are Genetically Heterogeneous

Valeria Difilippo, Karim H. Saba, Emelie Styring, Linda Magnusson, Jenny Nilsson, Michaela Nathrath, Daniel Baumhoer, Karolin H. Nord

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Osteosarcoma is the most common primary bone malignancy, often detected in children and adolescents and commonly associated with TP53 alterations along with a high number of chromosomal rearrangements. However, osteosarcoma can affect patients of any age, and some tumors display less genetic complexity. Besides TP53 variants, data on key driving mutations are lacking for many osteosarcomas, particularly those affecting adults. To detect osteosarcoma-specific alterations, we screened transcriptomic and genomic sequencing and copy number data from 150 bone tumors originally diagnosed as osteosarcomas. To increase the precision in gene fusion detection, we developed a bioinformatic tool denoted as NAFuse, which extracts gene fusions that are verified at both the genomic and transcriptomic levels. Apart from the already reported genetic subgroups of osteosarcoma with TP53 structural variants, or MDM2 and/or CDK4 amplification, we did not identify any recurrent genetic driver that signifies the remaining cases. Among the plethora of mutations identified, we found genetic alterations characteristic of, or similar to, those of other bone and soft tissue tumors in 8 cases. These mutations were found in tumors with relatively few other genetic alterations or in adults. Due to the lack of clinical context and available tissue, we can question the diagnosis only on a genetic basis. However, our findings support the notion that osteosarcomas with few chromosomal alterations or adult onset seem genetically distinct from conventional osteosarcomas of children and adolescents.

Original languageEnglish
Article number100283
JournalLaboratory Investigation
Issue number1
StatePublished - Jan 2024
Externally publishedYes


  • NAFuse
  • bone tumor
  • gene fusion
  • osteosarcoma
  • sarcoma
  • soft tissue tumor


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