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Cancer

A changing global view

Global gene-expression profiles have emerged as a way to divide tumours that look similar into subgroups with distinct prognoses. But they can be technically demanding and difficult to implement as a routine clinical assay. Siavash Kurdistani and colleagues show elsewhere in this issue (Nature 435, 1262–1266; 2005) that taking a different global view — of histone modification — can provide a similar indicator, for prostate cancer at least, that may translate easily to the clinic.

Credit: DAVID SELIGSON

Histone proteins, around which DNA is wrapped to pack it into the nucleus, can be chemically modified in several places by the addition of acetyl or methyl groups. These modifications are reversible and can affect the expression of the associated genes. Cancer cells are known to have unusual patterns of histone modification, but so far work has focused on individual genes and their contribution to cancer development and progression.

In contrast, Kurdistani and colleagues looked at global levels of the acetylation or methylation of five different residues in histones H3 and H4 in prostate tumour samples. They used antibodies that were specific for each modification to highlight any differences; for example, the photo here shows a section of low-grade prostate cancer tissue (Gleason score 6) stained with an antibody against dimethylated arginine 3 of histone H4.

The authors found, from two independent sets of prostate cancer samples, that histone modification patterns can forecast the risk that a low-grade tumour will recur after surgical removal. How the observed global changes in histone modifications relate to the regulation of genes relevant to prostate cancer development is not known. However, using immunochemistry to detect bulk histone modifications in cancer samples is relatively easy, so these findings could be translated directly into prognostic markers for clinical use.

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