The lonely driver or the orchestra of mutations? How next generation sequencing datasets contradict the concept of single driver checkpoint mutations in solid tumours - NSCLC as a scholarly example.

Driver mutations are considered to be responsible for the majority of cancers and several of those mutations provide targets in order to set up personalized therapies. So far the generally accepted opinion had been that driver mutations occur as stand-alone factors, but novel sequencing technologies induced an essential rethink. Next generation sequencing approaches have shown that double, triple or multiple concurrent mutations could occur within the same tumour and may by interaction influence sensitivity to anticancer drugs and therapy success. This review focusses on this novel concept and discusses the challenges for molecular pathology and laboratory diagnostics while providing putative solutions to overcome the present pitfalls, thereby taking NSCLC as an example.