Cancer arises as a consequence of transforming ‘driver' mutations able to initiate tumour formation. Upon tumour initiation, positive selection and clonal progression further leads to the accumulation of ‘passenger' mutations conferring additional growth advantages. Identification of driver mutations might therefore allow not only for the establishment of targeted therapies but also, most importantly, for the elucidation and targeting of the early events underlying cancer formation. Although enormous progress has been made, current bioinformatics approaches tend to focus on diver mutations found in high frequencies while underestimating the role that low frequency mutations might play during carcinogenesis404142434445.
