The EACR’s Top 10 Cancer Research Publications is a regular summary of the most interesting and impactful recent papers in cancer research. It is curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided to us by the authors.
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S.Y. Shen, R. Singhania, G. Fehringer, A. Chakravarthy et al., Nature volume 563, pages 579–583 (2018)
Summary
Most approaches to detect circulating tumour DNA (ctDNA) currently focus on cancer-associated somatic mutations. However, there is only a small number of recurrent mutations available which limit its sensitivity. In addition, somatic alterations alone cannot identify tissue-of-origin. Shen et al., provides a novel method to profile DNA methylation in plasma cfDNA termed cfMeDIP-seq (cell-free methylated DNA immunoprecipitation and high-throughput sequencing). This novel approach captures all methylated cfDNA then followed by sequencing. It has technical advantages by circumventing DNA degradation and reducing risk of false methylated signal, which is common in bisulfite conversion methods, while being cost efficient, as only methylated fragments are sequenced. It also has biological advantages, as it depends on DNA methylation profiles, which are tissue-specific and cancer-specific, and leverages thousands of recurrent DNA methylation changes that frequently occur in most cancer types. Shen et al., validated cfMeDIP-seq in a collection of plasma cfDNA from healthy donors and seven different cancer types (PDAC, AML, CRC, Renal, bladder, breast and Lung cancers). Using a machine learning-based approach, they were able to accurately classify multiple cancer types. Moreover, the classifier performed well in an independent validation set of healthy controls (AUROC: 0.969), Lung Cancer (AUROC: 0.971), AML (AUROC: 0.980), and PDAC (AUROC: 0.918).
Future impacts of the findings
Shen et al., reported a proof-of-concept study that genome-wide DNA methylation profiling of plasma cfDNA can be used for highly sensitive cancer detection and classification. Further independent validation is warranted to assess clinical validity of cfMeDIP-seq. If successful, this approach could be important in the liquid biopsy toolbox for cancer early detection, monitoring of treatment response and residual disease. Finally, since DNA methylation is tissue-specific, this approach could potentially have applications beyond oncology, to detect or monitor any disease associated with tissue damage and release of tissue-specific cfDNA into the circulation.
