The last years have seen conceptual and technical advances uncovering epigenetic pathways which present promising targets for diagnostic and therapeutic strategies in an increasing number of solid tumors and leukemias. Epigenetic modifi cations which promote the malignant potential of stem cells or respective progenitor cells are gaining an increased importance in malignancies of the elderly, when effects of environmental exposures, lifestyles and metabolism have left their traces in the genome and the associated protein components of the chromatin. This explains that besides " classic " tumor suppressor genes (e.g., of the P53 pathway), expression patterns of hormone receptors such as estrogen receptor and growth factor receptors, vitamin response, DNA -repair and apoptotic pathways (death associated protein kinase) are altered by epigenetic mechanisms in tumor cells. An insight into these complex mechanisms presents the basis for improved models which outline the chances and risks of therapeutic interventions combining chromatin -targeting drugs.
IntroductionDespite major advances in understanding key molecular lesions in cellular control pathways that contribute to cancer, it remains true that microscopic examination of nuclear structure is a gold standard in cancer diagnosis. Changes in the nuclear architecture, which largely involve the state of chromatin confi guration, have the potential to confi rm the cancer phenotype in a single cell. The most important cues are the size of the nucleus, nuclear outline, a condensed nuclear membrane, prominent nucleoli, dense " hyperchromatic " chromatin and a high nuclear/cytoplasmic ratio. Such structural features, visible under a microscope, likely correlate with profound alterations in chromatin function and resultant changes in gene expression states and/or chromosomal stability. Linking changes observable at a and