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Germline–epigenome crosstalk promotes aggressive subsets of prostate tumours

Nature Reviews Urology volume 16, page 693 (2019)Cite this article

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Germline and epigenetic crosstalk in primary prostate tumours could help to identify biomarkers of aggressive disease to improve patient stratification and optimize therapy assignation, according to new data published in Nature Medicine.

A number of factors contribute to prostate oncogenesis, including germline, epigenetic and environmental changes, which ultimately result in the dysregulation of cellular processes that is characteristic of malignancy. Genome-wide association studies (GWAS) have identified >100 germline variants associated with an increased risk of cancer diagnosis. However, although these data suggest that germline single-nucleotide polymorphisms (SNPs) could cause development of aggressive tumours, GWAS have failed to identify robust associations with specific loci; modulation of the epigenome via SNPs might explain this discrepancy and provide the missing link. Some germline alterations in tumour-suppressor genes — such as RB1, APC, BRCA1 and BRCA2 — can induce epigenomic changes, which can further affect oncogenesis. Tumours are able to hijack epigenetic regulatory systems to silence tumour suppressors, rewiring DNA methylation. Enrichment of susceptibility loci at regulatory regions can modulate the epigenome, increasing tumour aggressiveness. Thus, co-analysis of the germ line and methylation might identify loci involved in tumorigenesis that did not previously reach significance that could provide biomarkers and inform the development of aggressive disease.

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References

Original article

  • Houlahan, K. E. et al. Genome-wide germline correlates of the epigenetic landscape of prostate cancer. Nat. Med. 25, 1615–1626 (2019)

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  1. Nature Reviews Urology http://www.nature.com/nrurol/

    Annette Fenner

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  1. Annette Fenner
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Correspondence to Annette Fenner.

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Fenner, A. Germline–epigenome crosstalk promotes aggressive subsets of prostate tumours. Nat Rev Urol 16, 693 (2019). https://doi.org/10.1038/s41585-019-0254-7

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  • DOI: https://doi.org/10.1038/s41585-019-0254-7

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