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Case Reports
. 2014 Dec 11;8(1):20.
doi: 10.1186/s40246-014-0020-0.

Whole exome sequencing of a single osteosarcoma case--integrative analysis with whole transcriptome RNA-seq data

Ene Reimann  1   2 , Sulev Kõks  3   4 , Xuan Dung Ho  5   6 , Katre Maasalu  7   8 , Aare Märtson  9   10
Affiliations
Case Reports

Whole exome sequencing of a single osteosarcoma case--integrative analysis with whole transcriptome RNA-seq data

Ene Reimann et al. Hum Genomics. .

Abstract

Background: Osteosarcoma (OS) is a prevalent primary malignant bone tumour with unknown etiology. These highly metastasizing tumours are among the most frequent causes of cancer-related deaths. Thus, there is an urgent need for different markers, and with our study, we were aiming towards finding novel biomarkers for OS.

Methods: For that, we analysed the whole exome of the tumorous and non-tumour bone tissue from the same patient with OS applying next-generation sequencing. For data analysis, we used several softwares and combined the exome data with RNA-seq data from our previous study.

Results: In the tumour exome, we found wide genomic rearrangements, which should qualify as chromotripsis-we detected almost 3,000 somatic single nucleotide variants (SNVs) and small indels and more than 2,000 copy number variants (CNVs) in different chromosomes. Furthermore, the somatic changes seem to be associated to bone tumours, whereas germline mutations to cancer in general. We confirmed the previous findings that the most significant pathway involved in OS pathogenesis is probably the WNT/β-catenin signalling pathway. Also, the IGF1/IGF2 and IGF1R homodimer signalling and TP53 (including downstream tumour suppressor gene EI24) pathways may have a role. Additionally, the mucin family genes, especially MUC4 and cell cycle controlling gene CDC27 may be considered as potential biomarkers for OS.

Conclusions: The genes, in which the mutations were detected, may be considered as targets for finding biomarkers for OS. As the study is based on a single case and only DNA and RNA analysis, further confirmative studies are required.

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Figures

Figure 1
Figure 1
Circos plot illustrating the CNVs and LOHs in the OS tissue compared to that in the control tissue. CNVs are marked as lines in the centre: red—gain and green—loss. LOHs are marked as dots in the centre: black—copy neutral, green—copy gain and red—copy loss.
Figure 2
Figure 2
The CNVs in chromosomes 2 and 19 in the osteosarcoma tissue compared to that in the control tissue. Data analysis performed with CEQer software.
See this image and copyright information in PMC

References

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