Location, location, location

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Science  09 Sep 2016:
Vol. 353, Issue 6304, pp. 1095-1096
DOI: 10.1126/science.aai7629

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There was a time when cancers were almost entirely defined by their tissue of origin. Patients were diagnosed with a cancer of a particular organ and treated—with varying degrees of success—according to these classifications. However, research over the past 50 years has revolutionized our understanding of malignant progression at the genomic level and established the view that cancers could also be grouped by the genetic alterations that drove their development. While this work has uncovered a bewildering complexity of genetic and epigenetic alterations in tumors, it also showed that mutations in the same oncogenes and tumor suppressor genes are found time and again in multiple types of cancer. These driver mutations play a fundamental causative role in the development of almost all cancers, suggesting that under the hood, even cancers of diverse origins have key similarities. An extension of this concept is that the presence of frequently occurring genetic drivers can be used to dictate the optimal therapeutic approach, regardless of whether the tumor derives from breast, lung, colon, or pancreas. While such reductionism is attractive, it remains clear that cancers from different organs are dissimilar in many important ways. Now, on page 1161 of this issue, Mayers et al. (1) provide further evidence that the tissue of origin is as important as the driving oncogenic mutations in determining how a tumor behaves and—by extension—how to treat it.