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Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data
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 no...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272536/ https://www.ncbi.nlm.nih.gov/pubmed/25496518 http://dx.doi.org/10.1186/s40246-014-0020-0 |
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author | Reimann, Ene Kõks, Sulev Ho, Xuan Dung Maasalu, Katre Märtson, Aare |
author_facet | Reimann, Ene Kõks, Sulev Ho, Xuan Dung Maasalu, Katre Märtson, Aare |
author_sort | Reimann, Ene |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40246-014-0020-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4272536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42725362014-12-21 Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data Reimann, Ene Kõks, Sulev Ho, Xuan Dung Maasalu, Katre Märtson, Aare Hum Genomics Primary Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40246-014-0020-0) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-11 /pmc/articles/PMC4272536/ /pubmed/25496518 http://dx.doi.org/10.1186/s40246-014-0020-0 Text en © Reimann et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Primary Research Reimann, Ene Kõks, Sulev Ho, Xuan Dung Maasalu, Katre Märtson, Aare Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data |
title | Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data |
title_full | Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data |
title_fullStr | Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data |
title_full_unstemmed | Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data |
title_short | Whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome RNA-seq data |
title_sort | whole exome sequencing of a single osteosarcoma case—integrative analysis with whole transcriptome rna-seq data |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272536/ https://www.ncbi.nlm.nih.gov/pubmed/25496518 http://dx.doi.org/10.1186/s40246-014-0020-0 |
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