Cancer Genetics and Epigenetics 2024, Vol.12, No.2, 79-87 http://medscipublisher.com/index.php/cge 83 4.3 Cost and accessibility The high cost of WGS remains a significant barrier to its widespread adoption in clinical practice. Despite advances in sequencing technologies that have reduced costs, WGS is still expensive compared to other genomic testing methods, such as targeted sequencing or panel-based approaches (Beltran et al., 2013; Imieliński et al., 2017). This cost factor limits accessibility, particularly in resource-limited settings, and raises questions about the cost-effectiveness of WGS in routine clinical care. Additionally, the infrastructure required for WGS, including bioinformatics support and data storage, adds to the overall expense and complexity of implementing WGS in clinical settings (Abida et al., 2017; Imieliński et al., 2017). Efforts to reduce costs and improve the efficiency of WGS are essential to make this technology more accessible and practical for widespread clinical use. 5 Future Prospects and Research Directions 5.1 Technological advancements 5.1.1 Emerging technologies in genome sequencing The field of whole-genome sequencing is rapidly evolving, with significant advancements in next-generation sequencing (NGS) technologies. These advancements have enabled more comprehensive and detailed analyses of cancer genomes, including prostate cancer. Emerging technologies such as deep WGS and liquid biopsy techniques are particularly promising. For instance, deep WGS of circulating tumor DNA (ctDNA) has shown potential in revealing the clonal architecture and evolution of treatment-resistant prostate cancer, providing insights into the heterogeneity of ctDNA populations compared to metastatic tissue (Herberts et al., 2022; Weiss et al., 2022). Additionally, the development of scalable NGS systems, such as the Oncomine Comprehensive Panel, has facilitated the detection of relevant somatic variants in solid tumors, including prostate cancer, using minimal DNA/RNA from formalin-fixed paraffin-embedded (FFPE) tissues (Hovelson et al., 2015; Liang et al., 2019). 5.1.2 Potential improvements in WGS accuracy and efficiency Despite the progress, there are still substantial improvements to be made in sequencing technologies, informatics, and computational resources to enhance the accuracy and efficiency of WGS. Current WGS platforms are considered primitive, and there is a need for better integration of multi-omics data, functional data, and clinical-pathological data to fully interpret the diverse cancer genomes and phenotypes (Nakagawa et al., 2015; Nakagawa and Fujita, 2018). Moreover, the feasibility of WGS in routine clinical practice has been demonstrated, but challenges such as low tumor purity and the need for fresh-frozen samples instead of FFPE samples need to be addressed to improve the success rate and turnaround time of WGS (Samsom et al., 2022). 5.2 Integrative approaches 5.2.1 Combining WGS with other omics technologies Integrative approaches that combine WGS with other omics technologies, such as transcriptomics, epigenomics, and immunogenomics, are essential for a comprehensive understanding of cancer biology. For example, integrating WGS data with RNA-Seq, epigenomics, and clinical-pathological information can help elucidate the functional or clinical implications of unexplored genomic regions and mutational signatures in cancer genomes (Nakagawa and Fujita, 2018; Rubin and Demichelis, 2018). Additionally, ctDNA nucleosome footprinting has been used to infer mRNA abundance in metastatic lesions, demonstrating the potential of combining WGS with transcriptomic data to understand the transcriptomic patterns in prostate cancer (Herberts et al., 2022). 5.2.2 Benefits of integrative cancer genomics The benefits of integrative cancer genomics are manifold. By combining WGS with other omics data, researchers can identify new genomic alterations and clinically actionable aberrations that could impact treatment decisions. For instance, a multi-institutional clinical sequencing infrastructure for metastatic castration-resistant prostate cancer (mCRPC) identified frequent aberrations in AR, ETS genes, TP53, and PTEN, as well as new genomic alterations in PIK3CA/B, BRAF/RAF1, and other cancer-related genes (Robinson et al., 2015). Such integrative approaches can provide a more comprehensive understanding of the genomic landscape of prostate cancer and facilitate the development of precision medicine frameworks.
RkJQdWJsaXNoZXIy MjQ4ODYzNQ==