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Osteosarcomas With Few Chromosomal Alterations or Adult Onset Are Genetically Heterogeneous

Difilippo, Valeria LU ; Saba, Karim H. LU orcid ; Styring, Emelie LU ; Magnusson, Linda LU ; Nilsson, Jenny LU ; Nathrath, Michaela ; Baumhoer, Daniel and Nord, Karolin H. LU (2024) In Laboratory investigation; a journal of technical methods and pathology 104(1).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bone tumor, gene fusion, NAFuse, osteosarcoma, sarcoma, soft tissue tumor
in
Laboratory investigation; a journal of technical methods and pathology
volume
104
issue
1
publisher
Nature Publishing Group
external identifiers
  • pmid:37931683
  • scopus:85182955511
ISSN
1530-0307
DOI
10.1016/j.labinv.2023.100283
language
English
LU publication?
yes
id
a89ba048-b071-432c-8ead-0a302f7523ff
date added to LUP
2024-02-19 15:00:26
date last changed
2024-04-19 17:03:44
@article{a89ba048-b071-432c-8ead-0a302f7523ff,
  abstract     = {{<p>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.</p>}},
  author       = {{Difilippo, Valeria and Saba, Karim H. and Styring, Emelie and Magnusson, Linda and Nilsson, Jenny and Nathrath, Michaela and Baumhoer, Daniel and Nord, Karolin H.}},
  issn         = {{1530-0307}},
  keywords     = {{bone tumor; gene fusion; NAFuse; osteosarcoma; sarcoma; soft tissue tumor}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Laboratory investigation; a journal of technical methods and pathology}},
  title        = {{Osteosarcomas With Few Chromosomal Alterations or Adult Onset Are Genetically Heterogeneous}},
  url          = {{http://dx.doi.org/10.1016/j.labinv.2023.100283}},
  doi          = {{10.1016/j.labinv.2023.100283}},
  volume       = {{104}},
  year         = {{2024}},
}