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

Sci Rep. 2021 Jan 12;11(1):667. doi: 10.1038/s41598-020-79648-6.

Authors

Ana Cristina Vargas^{1

2

3}, Lesley-Ann Gray⁴, Christine L White^{5

6}, Fiona M Maclean^{7

8

9}, Peter Grimison^{10

11}, Nima Mesbah Ardakani^{12

13}, Fiona Bonar⁷, Elizabeth M Algar^{5

6}, Alison L Cheah⁷, Peter Russell¹⁰, Annabelle Mahar¹⁴, Anthony J Gill^{8

10

15}

Affiliations

¹ Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park, NSW, 2113, Australia. cvargas@dhm.com.au.
² Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia. cvargas@dhm.com.au.
³ Medical School, University of Sydney, Sydney, NSW, 2006, Australia. cvargas@dhm.com.au.
⁴ Australian Genome Research Facility Ltd, Victorian Comprehensive Cancer Centre, Melbourne, VIC, 3000, Australia.
⁵ Genetics and Molecular Pathology Laboratory, Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
⁶ Monash University, Clayton, VIC, Australia.
⁷ Department of Anatomical Pathology, Douglass Hanly Moir Pathology, Macquarie Park, NSW, 2113, Australia.
⁸ Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia.
⁹ Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
¹⁰ Medical School, University of Sydney, Sydney, NSW, 2006, Australia.
¹¹ Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, 2050, Australia.
¹² Department of Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Perth, WA, Australia.
¹³ School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia.
¹⁴ Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia.
¹⁵ NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, 2065, Australia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Biomarkers, Tumor / genetics*
DNA Methylation*
Epigenesis, Genetic*
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Humans
Male
Middle Aged
Neoplasm Metastasis / genetics
Neoplasm Metastasis / pathology*
Neoplasm Recurrence, Local / genetics
Neoplasm Recurrence, Local / pathology*
Prognosis
Sarcoma / genetics
Sarcoma / pathology*

Substances

Biomarkers, Tumor