Recurrent driver mutations in benign tumors

The understanding of the molecular pathogenesis of benign tumors may bring essential information to clarify the process of tumorigenesis, and ultimately improve the understanding of events such as malignant transformation. The definition of benign neoplasia is not always straightforward and herein the issues surrounding this concept are discussed. Benign neoplasms share all cancer hallmarks with malignancies, except for metastatic potential. Recently, next-generation sequencing has provided unprecedented opportunities to unravel the genetic basis of benign neoplasms and, so far, we have learned that benign neoplasms are indeed characterized by the presence of genetic mutations, including genes rearrangements. Driver mutations in advanced cancer are those that confer growth advantage, and which have been positively selected during cancer evolution. Herein, some discussion will be brought about this concept in the context of cancer prevention, involving precursor lesions and benign neoplasms. When considering early detection and cancer prevention, a driver mutation should not only be advantageous (i.e., confer survival advantage), but predisposing (i.e., promoting a cancer phenotype). By including the benign counterparts of malignant neoplasms in tumor biology studies, it is possible to evaluate the risk posed by a given mutation and to differentiate advantageous from predisposing mutations, further refining the concept of driver mutations. Therefore, the study of benign neoplasms should be encouraged because it provides valuable information on tumorigenesis central for understanding the progression from initiation to malignant transformation.