Editors' ChoiceCancer

Molecular Cancer Screening Comes Alive

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Science Translational Medicine  30 Mar 2011:
Vol. 3, Issue 76, pp. 76ec44
DOI: 10.1126/scitranslmed.3002426

One of the holy grails of medicine is the ability to predict an individual’s risk for developing cancer. Although genetic screening is available for several genetic cancer syndromes, such as those associated with BRCA-1 and BRCA-2 mutations, genetic screening tools remain unavailable for most other common cancers. The fundamental challenges of any screening test are ease of use and cost-effectiveness at the population level. Marsit et al. address these issues by performing epigenetic profiling for bladder cancer using peripheral blood.

In their paper, the authors performed genome-wide screening of the changes in methylation pattern associated with bladder cancer using nonmalignant tissue: in this case, peripheral blood. Traditionally, epigenetic alterations in DNA methylation occur in malignant tumor tissue. It was not known previously whether unique epigenetic alterations occurred in nonmalignant tissue or whether early epigenetic changes could be used to predict development of malignancy. Using a training set of over 100 cases of bladder cancer and matched controls, nine CpG islands with distinct methylation pattern changes were identified in association with bladder cancer; these findings were then validated in a separate set of bladder cancer patients and controls. In combination with traditional bladder cancer risk factors such as age, sex, smoking, and family history, this new model was able to predict bladder cancer correctly ~76% of the time. These results could have a profound impact on the future of molecular screening. However, as the authors themselves point out, the timing of these changes in the course of bladder cancer development cannot be determined in this retrospective study, leaving open the question of whether these epigenetic changes will be clinically useful for prognosis. Moreover, this type of analysis may be cost-prohibitive if performed with a large population of patients. Nevertheless, the dawn of molecular screening may soon lead to a new day.

C. J. Marsit et al., DNA methylation array analysis identifies profiles of blood-derived DNA methylation associated with bladder cancer. J. Clin. Oncol. 29, 1133–1139 (2011). [Abstract]

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