The Cancer Genome in the Long Reads Era.

Cancer genomics, driven by advancements in sequencing technologies, is rapidly transforming our understanding of tumor biology. The advent of high-throughput short-read sequencing technologies has enabled a paradigm shift in cancer genomics, providing unprecedented resolution of mutations that drive tumorigenesis. Initially, short-read sequencing dominated the field, revealing the repertoire of mutational signatures and the complexities of tumor heterogeneity. However, the inherent limitations of short-read sequencing, particularly in resolving complex structural variations and repetitive regions, underscored the need for alternative approaches. This chapter delves into the transformative potential of long-read sequencing in overcoming these limitations, ushering in a new era for cancer genomics. By spanning larger genomic regions, long-reads offer a more comprehensive view of structural variations, phasing information, and complex rearrangements, crucial for deciphering the evolutionary trajectories of cancer. Furthermore, the chapter examines the dynamics of somatic evolution, comparing Darwinian and non-Darwinian frameworks, and discusses how these models inform our understanding of cancer progression which have implications for cancer therapies. Finally, a bioinformatics workflow, leveraging long-read sequencing data, is outlined to enable the identification of cancer-associated mutations. Integrating cutting-edge sequencing technologies with advanced computational approaches is essential for accelerating oncological research and improving cancer therapies. Long-read sequencing is poised to unveil the complex genomic architecture of cancers, potentially leading to more precise and effective treatments.