Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease

Ana Cristina Vargas; Lesley Ann Gray; Christine L. White; Fiona M. Maclean; Peter Grimison; Nima Mesbah Ardakani; Fiona Bonar; Elizabeth M. Algar; Alison L. Cheah; Peter Russell; Annabelle Mahar; Anthony J. Gill

doi:10.1038/s41598-020-79648-6

Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease

Ana Cristina Vargas^*, Lesley Ann Gray, Christine L. White, Fiona M. Maclean, Peter Grimison, Nima Mesbah Ardakani, Fiona Bonar, Elizabeth M. Algar, Alison L. Cheah, Peter Russell, Annabelle Mahar, Anthony J. Gill

^*Corresponding author for this work

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Abstract

In this study we used the Illumina Infinium Methylation array to investigate in a cohort of matched archival human tissue samples (n = 32) from 14 individuals with soft tissue sarcomas if genome-wide methylation changes occur during metastatic and recurrent (Met/Rec) disease. A range of sarcoma types were selected for this study: leiomyosarcoma (LMS), myxofibrosarcoma (MFS), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). We identified differential methylation in all Met/Rec matched samples, demonstrating that epigenomic differences develop during the clonal evolution of sarcomas. Differentially methylated regions and genes were detected, not been previously implicated in sarcoma progression, including at PTPRN2 and DAXX in LMS, WT1-AS and TNXB in SS, VENTX and NTRK3 in pleomorphic RMS and MEST and the C14MC / miR-379/miR-656 in MFS. Our overall findings indicate the presence of objective epigenetic differences across primary and Met/Rec human tissue samples not previously reported.

Original language	English
Article number	667
Pages (from-to)	1-17
Number of pages	17
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-79648-6
Publication status	Published - 12 Jan 2021

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Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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Vargas, A. C., Gray, L. A., White, C. L., Maclean, F. M., Grimison, P., Ardakani, N. M., Bonar, F., Algar, E. M., Cheah, A. L., Russell, P., Mahar, A., & Gill, A. J. (2021). Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease. Scientific Reports, 11(1), 1-17. [667]. https://doi.org/10.1038/s41598-020-79648-6

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title = "Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease",

abstract = "In this study we used the Illumina Infinium Methylation array to investigate in a cohort of matched archival human tissue samples (n = 32) from 14 individuals with soft tissue sarcomas if genome-wide methylation changes occur during metastatic and recurrent (Met/Rec) disease. A range of sarcoma types were selected for this study: leiomyosarcoma (LMS), myxofibrosarcoma (MFS), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). We identified differential methylation in all Met/Rec matched samples, demonstrating that epigenomic differences develop during the clonal evolution of sarcomas. Differentially methylated regions and genes were detected, not been previously implicated in sarcoma progression, including at PTPRN2 and DAXX in LMS, WT1-AS and TNXB in SS, VENTX and NTRK3 in pleomorphic RMS and MEST and the C14MC / miR-379/miR-656 in MFS. Our overall findings indicate the presence of objective epigenetic differences across primary and Met/Rec human tissue samples not previously reported.",

author = "Vargas, {Ana Cristina} and Gray, {Lesley Ann} and White, {Christine L.} and Maclean, {Fiona M.} and Peter Grimison and Ardakani, {Nima Mesbah} and Fiona Bonar and Algar, {Elizabeth M.} and Cheah, {Alison L.} and Peter Russell and Annabelle Mahar and Gill, {Anthony J.}",

note = "Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

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Vargas, AC, Gray, LA, White, CL, Maclean, FM, Grimison, P, Ardakani, NM, Bonar, F, Algar, EM, Cheah, AL, Russell, P, Mahar, A & Gill, AJ 2021, 'Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease', Scientific Reports, vol. 11, no. 1, 667, pp. 1-17. https://doi.org/10.1038/s41598-020-79648-6

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AU - Vargas, Ana Cristina

AU - Gray, Lesley Ann

AU - White, Christine L.

AU - Maclean, Fiona M.

AU - Grimison, Peter

AU - Ardakani, Nima Mesbah

AU - Bonar, Fiona

AU - Algar, Elizabeth M.

AU - Cheah, Alison L.

AU - Russell, Peter

AU - Mahar, Annabelle

AU - Gill, Anthony J.

N1 - Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2021/1/12

Y1 - 2021/1/12

N2 - In this study we used the Illumina Infinium Methylation array to investigate in a cohort of matched archival human tissue samples (n = 32) from 14 individuals with soft tissue sarcomas if genome-wide methylation changes occur during metastatic and recurrent (Met/Rec) disease. A range of sarcoma types were selected for this study: leiomyosarcoma (LMS), myxofibrosarcoma (MFS), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). We identified differential methylation in all Met/Rec matched samples, demonstrating that epigenomic differences develop during the clonal evolution of sarcomas. Differentially methylated regions and genes were detected, not been previously implicated in sarcoma progression, including at PTPRN2 and DAXX in LMS, WT1-AS and TNXB in SS, VENTX and NTRK3 in pleomorphic RMS and MEST and the C14MC / miR-379/miR-656 in MFS. Our overall findings indicate the presence of objective epigenetic differences across primary and Met/Rec human tissue samples not previously reported.

AB - In this study we used the Illumina Infinium Methylation array to investigate in a cohort of matched archival human tissue samples (n = 32) from 14 individuals with soft tissue sarcomas if genome-wide methylation changes occur during metastatic and recurrent (Met/Rec) disease. A range of sarcoma types were selected for this study: leiomyosarcoma (LMS), myxofibrosarcoma (MFS), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). We identified differential methylation in all Met/Rec matched samples, demonstrating that epigenomic differences develop during the clonal evolution of sarcomas. Differentially methylated regions and genes were detected, not been previously implicated in sarcoma progression, including at PTPRN2 and DAXX in LMS, WT1-AS and TNXB in SS, VENTX and NTRK3 in pleomorphic RMS and MEST and the C14MC / miR-379/miR-656 in MFS. Our overall findings indicate the presence of objective epigenetic differences across primary and Met/Rec human tissue samples not previously reported.

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Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease

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