Clinical oncology and pathological diagnostics regard cancer as an organ- and tissue-specific disease. Comprehensive mutational profiling information from next-generation sequencing projects may be used to study to what extent the anatomic tumor classifications relate to the observed molecular profiles. Here, we review data that show substantial genetic similarities across major anatomic cancer types and that propose novel tumor classifications based on mutational profiling. Although these studies provide important insight into molecular tumor properties and some even propose novel tumor classification systems, current clinical evidence is lacking that genetic tumor profiling is sufficient to replace histological tumor typing. Recent studies rather show that targeted treatments efficaceous in one tumor type are not necessarily successful in another despite the presence of the same (actionable) mutations. We discuss the implications of the observed complex mutational tumor profiles for targeted therapy selection and future trial design in precision oncology.
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