Journal article

Genome-wide plasma DNA methylation features of metastatic prostate cancer

Anjui Wu, Paolo Cremaschi, Daniel Wetterskog, Vincenza Conteduca, Gian Marco Franceschini, Dimitrios Kleftogiannis, Anuradha Jayaram, Shahneen Sandhu, Stephen Q Wong, Matteo Benelli, Samanta Salvi, Giorgia Gurioli, Andrew Feber, Mariana Buongermino Pereira, Anna Maria Wingate, Enrique Gonzalez-Billalebeitia, Ugo De Giorgi, Francesca Demichelis, Stefano Lise, Gerhardt Attard

Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2020

Abstract

Tumor DNA circulates in the plasma of cancer patients admixed with DNA from noncancerous cells. The genomic landscape of plasma DNA has been characterized in metastatic castration-resistant prostate cancer (mCRPC) but the plasma methylome has not been extensively explored. Here, we performed next-generation sequencing (NGS) on plasma DNA with and without bisulfite treatment from mCRPC patients receiving either abiraterone or enzalutamide in the pre- or post-chemotherapy setting. Principal component analysis on the mCRPC plasma methylome indicated that the main contributor to methylation variance (principal component one, or PC1) was strongly correlated with genomically determined tumor fract..

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Grants

Awarded by Cancer Research UK Advanced Clinician Scientist fellowship


Awarded by MRC Clinical Research fellowship


Funding Acknowledgements

This work was funded by a Prostate Cancer Foundation Challenge Award, the John Black Charitable Foundation, and a Cancer Research UK Advanced Clinician Scientist fellowship (grant A22744). AJ is funded by an MRC Clinical Research fellowship (MR/P002072/1). We thank the participating men and their families who suffered from metastatic prostate cancer and nonetheless gave the gift of participation so that others might benefit. We thank the investigators of the Cancer Tissue Collection After Death (CASCADE) program in Melbourne, Australia; Karolina Nowakowska (UCL Cancer Institute) for culturing LNCaP, LNCaP95, and VCaP cell lines; and Alessandro Romanel (University of Trento) for analysis of plasma samples using CLONET. We acknowledge funding from the Taiwan Ministry of Education, the Bob Champion Cancer Trust, and the UK National Institutes for Health Research funding to the Royal Marsden, the Institute of Cancer Research Biomedical Research Centre, and the UCL Hospital's Biomedical Research Centre.