The article reviews the genomic landscapes of common forms of human cancer, highlighting the identification of approximately 140 genes that can promote tumorigenesis when altered by intragenic mutations. These "driver genes" are classified into 12 signaling pathways regulating cell fate, survival, and genome maintenance. The authors discuss the challenges in identifying and classifying driver genes, particularly those with subtle mutations, and propose a method based on mutation patterns rather than frequency. They also explore the concept of "dark matter," which refers to mutations that are difficult to detect due to technical limitations and epigenetic changes. The article emphasizes the importance of understanding these pathways for developing more effective cancer management strategies and highlights the impact of genome-based medicine on clinical care, such as the development of targeted therapies for specific mutations.The article reviews the genomic landscapes of common forms of human cancer, highlighting the identification of approximately 140 genes that can promote tumorigenesis when altered by intragenic mutations. These "driver genes" are classified into 12 signaling pathways regulating cell fate, survival, and genome maintenance. The authors discuss the challenges in identifying and classifying driver genes, particularly those with subtle mutations, and propose a method based on mutation patterns rather than frequency. They also explore the concept of "dark matter," which refers to mutations that are difficult to detect due to technical limitations and epigenetic changes. The article emphasizes the importance of understanding these pathways for developing more effective cancer management strategies and highlights the impact of genome-based medicine on clinical care, such as the development of targeted therapies for specific mutations.