DNA Methylation Biomarkers
Our research is focused on identifying DNA methylation changes associated with disease, in order to improve interpretation of diagnostic samples and guide treatment decisions.
Our current focus is on prostate cancer. In our most recent project we used whole genome sequencing technologies to characterise the distinct methylome of cells surrounding the prostate tumour. Excitingly we identified a subset of methylation changes shared by both tumour cells and surrounding cells in the tumour microenvironment. These shared changes hold promise to improve the diagnostic and prognostic sensitivity of biopsies.
In a new project, funded by Cancer Council NSW, we are working with clinicians to explore the utility of our prostate microenvironment methylation biomarkers to determine the presence of multi-focal tumours. The aim is to establish a test of patient suitability for focal therapy, a promising new form of treatment than is less aggressive than current surgical approaches in which the whole prostate is removed.
The group has also played a role in developing methods to measure DNA methylation. In particular in devising analytical methods and workflows for the analysis of DNA methylation microarray data, and it’s integration with sample-matched data from other next-generation sequencing technologies measuring gene expression (RNA-seq) and chromatin modifications (ChIP-seq). In ongoing work we are also optimising the laboratory work and bioinformatic analysis of targeted bisuflite sequencing in formalin-fixed biopsy samples.
Lam D*, Luu PL*, Song J, Qu W, Risbridger G, Lawrence M, Lu J, Trau M, Korbie D, Clark S, Pidsley R*, Stirzaker C*. (2020) Comprehensive Evaluation of Targeted Multiplex Bisulphite PCR sequencing for validation of DNA methylation biomarker panels. Clinical Epigenetics 12:90 doi:10.1186/s13148-020-00880-y
Lawrence M*, Pidsley R*, Niranjan B, Papargiris M, Pereira B, Richards M, Teng L, Norden S, Ryan A, Frydenberg M, Stirzaker C, Taylor R, Risbridger G*, Clark S*. (2020) Alterations in the methylome of the stromal tumour microenvironment signal the presence and severity of prostate cancer. Clinical Epigenetics 12:48 doi:10.1186/s13148-020-00836-2
Pidsley R, Stirzaker C. (2019) Cancer Methylation Biomarkers in circulating cell-free DNA. Invited book chapter in Clinical Epigenetics (pg. 217-245) published by Springer Nature.
Skvortsova K, Masle-Farquhar E, Luu P, Song J, Qu W, Zotenko E, Gould C, Du Q, Peters T, Colino Sanguino Y, Pidsley R, Nair S, Khoury A, Smith G, Miosge L, Reed J, Kench J, Rubin M, Horvath L, Bogdanovic O, Mei Lim S, Polo J, Goodnow C, Stirzaker C*, Clark S*. (2019) DNA hypermethylation encroachment at CpG island borders in cancer is predisposed by H3K4 monomethylation patterns. Cancer Cell 35(2):297-314.e8. doi:10.1016/j.ccell.2019.01.004
Peters T, French H, Bradford S, Pidsley R, Stirzaker C, Varinli H, Nair S, Qu W, Song J, Giles K, Statham A, Spiers H, Speed T, Clark S. (2018) Evaluation of cross-platform and interlaboratory concordance via consensus modeling of genomic measurements in genomic studies. Bioinformatics 35(4):560-570 doi:10.1093/bioinformatics/bty675
Pidsley R*, Lawrence M*, Zotenko E, Niranjan B, Statham A, Song J, Chabanon R, Qu W, Wang H, Richards M, Nair S, Armstrong N, Nim H, Papargiris M, Balanathan P, French H, Peters T, Norden S, Ryan A, Pedersen J, Kench J, Daly R, Horvath L, Stricker P, Frydenberg M, Taylor R, Stirzaker C, Risbridger G*, Clark S*. (2018) Enduring Epigenetic Landmarks Define the Cancer Microenvironment. Genome Research 28(5):625-638 doi:10.1101/gr.229070.117 Cover of Journal
Pidsley R*, Zotenko E*, Peters T, Lawrence M, Risbridger G, Molloy P, van Djik S, Muhlhausler B, Stirzaker C*, Clark S*. (2016) Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biology 17:208 doi: 10.1186/s13059-016-1066-1
Stirzaker C, Song J, Ng W, Du Q, Armstrong N, Locke W, Statham A, French H, Pidsley R, Valdes-Mora F, Zotenko E, Clark S. (2016) Methyl-CpG-Binding Protein MBD2 plays a key role in maintenance and spread of DNA methylation of CpG islands and shores in cancer. Oncogene 10.1038/onc.2016.297
Stone A, Zotenko E, Locke W, Korbie D, Millar E, Pidsley R, Stirzaker C, Graham P, Trau M, Musgrove E, Nicholson R, Gee J, Clark S. (2015) DNA methylation of oestrogen-regulated enhancers defines endocrine sensitivity in breast cancer. Nature Communications 6:7758 doi:10.1038/ncomms875,8
Peters T, Buckley M, Statham A, Pidsley R, Samaras K, Lord R, Clark S, Molloy P. (2015) De novo identification of differentially methylated regions in the human genome. Epigenetics & Chromatin 8 (1), 6 doi:10.1186/1756-8935-8-6
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